Genetic Polymorphisms Research Papers - Academia.edu (original) (raw)

Farmakogenomik dan Polimorfisme terhadap gen CYP2C19 menyebabkan kemampuan memetabolisme clopidogrel berkurang

Myostatin, encoded by the MSTN gene, is a strong regulator of skeletal muscle growth. The present study aimed to investigate whether the A55T and K153R polymorphisms of MSTN were associated with the strength training-induced muscle hypertrophy among Han Chinese men. A total of 94 healthy, untrained men were recruited for an 8-week strength training programme. The thicknesses of biceps and quadriceps, along with anthropometric measurements of the participants, were assessed before and after the programme. The MSTN polymorphisms were subsequently genotyped employing polymerase chain reaction-restriction fragment length polymorphism technique and confirmed by DNA sequencing. One-way analysis of variance was used to compare the pre- and post-training measurements between carriers of different polymorphic genotypes. Our results indicated that individuals with AT + TT genotype of the A55T polymorphism showed a significant increase in the thickness of biceps (0.292 ± 0.210 cm, P = 0.03), but not quadriceps (0.254 ± 0.198 cm, P = 0.07), compared to carriers of AA genotype. For the K153R polymorphism, the increases in the thicknesses of both biceps (0.300 ± 0.131 cm) and quadriceps (0.421 ± 0.281 cm) were significantly higher among individuals with KR than those with KK genotypes (P < 0.01 for both muscles). The results obtained therefore suggested a possible association between the two polymorphisms and the strength training-induced muscle hypertrophy among men of Han Chinese ethnicity.

Objectives: Genetic and archaeological research supports the theory that Arabia was the first region traversed by modern humans as they left Africa and dispersed throughout Eurasia. However, the role of Arabia from the initial migration out of Africa until more recent times is still unclear. Materials and Methods: We have generated 379 new hypervariable segment 1 (HVS-1) sequences from a range of geographic locations throughout Yemen. We compare these data to published HVS-1 sequences representing Ara-bia and neighboring regions to build a unique dataset of 186 populations and 14,290 sequences. Results: We identify 4,563 haplotypes unevenly distributed across Arabia and neighboring regions. Arabia contains higher proportions of shared haplotypes than the regions with which it shares these haplotypes, suggesting high levels of migration through the region. Populations in Arabia show higher levels of population expansion than those in East Africa, but lower levels than the Near East, Middle East or India. Arabian populations also show very high levels of genetic variation that overlaps with variation from most other regions. Conclusion: We take a population genetics approach to provide a comprehensive view of the relationships of Ara-bian and neighboring populations. We show that Arabian populations share closest links to the Near East and North Africa, but have a more ancient origin with slower demographic growth and/or lower migration rates. Our conclusions are supported by phylogenetic studies but also suggest that recent migrations have erased signals of earlier events. Am J Phys Anthropol 000:000–000, 2015. V C 2015 Wiley Periodicals, Inc.

Objective: To evaluate the prevalence of G6PD deficiency and characterize G202A, A376G and C563T polymorphisms in neonates using molecular assays. Methods: A total of one thousand samples were tested through quantitative analysis of enzyme activity, detecting 25 G6PD-deficient individuals. Patients identified as deficient were submitted to molecular analysis quantitative realtime polymerase chain reaction – (qPCR) to investigate the presence of variants associated with the deficiency. Results: The total prevalence of G6PD deficient was 2.5%. Of the 25 samples identified as deficient, 21 were submitted to qPCR assay to analyze the presence of G202A, A376G and C563T variants. All samples showed the G202A/A376G genotype, characterizing G6PD A- phenotype. Conclusion: The prevalence of G6PD deficiency in the present study was similar to that observed in other study populations in Brazil. Molecular analysis identified in all patients the presence of the genetic polymorphism G202A/A376G, more common in the Brazilian population with G6PD deficiency, which is directly estimated by enzyme activity level.

- by Siew Hua Gan
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- Pharmacokinetics, Genetic Polymorphisms, Tramadol, Pharmacodynamics
- by Siew Hua Gan
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- Genetic Polymorphisms, CYP3A4, Postoperative pain, Fentanyl

This study aimed to evaluate two XPD polymorphisms Asp312Asn (G→A) and Lys751Gln (A→C) in relation to the response to induction chemotherapy as well as the chemotherapy-induced toxicities in acute myeloid leukemia (AML) patients. This study included 51 Egyptian adult patients with newly diagnosed de novo cytogenetically normal AML of both sexes. A blood sample was collected from each patient, DNA was extracted and the two XPD polymorphisms (XPD Asp312Asn and XPD Lys751Gln) were determined using PCR-RFLP. Patients were treated by the standard remission induction protocol (3+7), during which they were monitored for possible chemotherapy-induced toxicities. Response to chemotherapy was evaluated after regeneration from bone marrow aplasia, patients who failed to achieve complete remission were subjected to a second course of chemotherapy. The results showed that XPD Asp312Asn polymorphism was not associated with the response to chemotherapy or with any of the studied chemotherapy-induced toxicities. On the other hand XPD Lys751Gln polymorphism, was associated with the response to chemotherapy and with cardiotoxicity but not with hepatotoxicity, nephrotoxicity or metabolic toxicity. Patients with the variant XPD 751 genotype (CC) were less likely to achieve complete remission and more likely to suffer chemotherapy-induced cardiotoxicity. This can be explained by the diminished DNA repair capacity in individuals carrying the CC genotype and the functional link between XPD and apoptosis.

- by Mohamed Barakat
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- Chemotherapy, DNA repair, Acute Myeloid Leukemia, Genetic Polymorphisms

Parkinson's disease is just a progressive disorder of the neural system that affects individual's movement. It develops slowly, sometimes beginning with barely obvious vibration in just one hand. But while a tremor could be the most recognized indication of Parkinson's disease, the disorder also generally causes hardness or slowing of movement. Type 2 diabetes referred to as adult-onset, is just an intense condition that affects the way in which the human body metabolizes sugar (glucose), the body's important supply of fuel.In this study, we evaluate of DISC1 gene rs3738401 polymorphism in Iranian Parkinson patients affected by type 2 Diabetes. The present research was conducted including number of 68Iranian Parkinson patients affected by type 2 Diabetes by employing ARMS-PCR process. To conclude, the information and statistics received from this study was analyzed by SPSS software. To sum up, the end outcome of current study explains considerable relation between DISC1 gene rs3738401 polymorphism in Iranian Parkinson patients affected by type 2 Diabetes. It could be an important genetic predisposition feature. INTRODUCTION Parkinson's disease (PD) is just a intense and progressive movement disorder, and thus symptoms continue and worsen over time [1]. The source is unknown, and though there is presently no treatment, you can find treatment methods for instance medication and surgery to control its symptoms. Parkinson's includes the malfunction and death of crucial nerve cells in the brain, named neurons. Parkinson's mainly affects neurons in a place of the brain labeled the substantia nigra [1,2]. Dopamine, a chemical that sends signals to the division of the brain that manages movement and skill. As PD progresses, the total amount of dopamine created in the brain decreases, leaving an individual unable to manage action normally[3]. Diabetes type 2 is a metabolic disease that is typified by hyperglycemia (high blood sugar) in the context of insulin resistance and relative lack of insulin. This really is in contrast to diabetes mellitus type 1, in which there's a complete insufficient insulin as a result of breakdown of islet cells in the pancreas.(4) The progress of type 2 diabetes is the result of a mixture of lifestyle and genetic factors. While some of those factors are under personal control, for example diet and obesity, other factors aren't, such as for instance increasing age, female sexual category, and genetics [5]. Deficiencies in sleep have been associated with type 2 diabetes. This really is believed to act through its effect on metabolism. The nutritional position of a mother during fetal development could also have a role, with one planned mechanism being that of altered DNA methylation [6]. Disrupted in schizophrenia 1 is just a protein which is encoded by the DISC1 gene in humans. In coordination with a wide collection of interacting partners, DISC1 has been demonstrated to take part in

- by Reza Mohammadhassan and +1
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- Polymorphism, Genetic Polymorphisms, DISC1, Parkinsons Disease

Objective: The human methylenetetrahydrofolate reductase (MTHFR) gene plays a crucial role in folate metabolism. Data regarding the influence of MTHFR gene polymorphisms on male fertility status are scarce and conflicting. We determined associations between 3 MTHFR gene polymorphisms (C677T, A1298C, and G1793A), serum folate, and total homocysteine (tHcy) levels, with male fertility status and semen parameters. Methods: MTHFR genotypes were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique and serum tHcy, folate, and vitamin B12 concentrations were measured in 164 men with idiopathic infertility and 328 healthy participants. Results: There was a significant difference in genotype frequency distribution of MTHFR C677T polymorphism between infertile patients and controls (P ¼ .004). The 677T allele carriers (TC or TT) had a significantly increased risk of infertility compared with the CC homozygotes (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.21-2.75, and OR ¼ 2.68, 95% CI ¼ 1.84-3.44, respectively), in a logistic regression model after adjustment for confounding factors. Men with the 677T, 1298C, and 1793G alleles showed significantly higher serum tHcy and lower folate levels (all Ps < .01). We found a positive correlation between serum folate concentrations and sperm density (r ¼ .74, P ¼ .001), percentage of sperm with progressive motility (r ¼ .68, P ¼ .001), as well as percentage of sperm with normal morphology (r ¼ .72, P ¼ .001). Conclusion: MTHFR C677T polymorphism is associated with an increased risk of idiopathic male infertility. Further study on the biologic role that this polymorphism plays in the development of infertility may lead to better understanding of the etiology of impaired spermatogenesis.

- by Mohammad Reza Safarinejad
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- Genetics, Urology, Andrology, Genetic Polymorphisms

transferrin (Tf) protein plays a crucial role in immunity against microbial pathogens like Escherichia coli, Streptococcus dysgalactiae, Streptococcus uberis, Staphylococcus aureus, and Streptococcus agalactiae those considered the main causes of mastitis in bovine. The effectiveness of transferrin protein lies in the prevention of microbial cells from getting iron. The study of polymorphisms and detection of the single nucleotide polymorphisms (SNPs) of Tf gene could support the description of the inheritance differences of mastitis resistance and milk production traits. In this study A14037G SNP has been detected and new SNP was observed (C14081T) of Tf gene (entron 8) in Holstein-Frisian cows in Iraq. DNA was collected from 165 cows and the sequencing technique was used to investigate the genetic variation of two SNPs, A14037G and C14081T respectively. The percentages of genotype distribution for the transferring gene in sample of cows were 23.64, 58.18 and 18.18 % for the genotypes AA, AG and GG respectively and the differences between these percentages were significant (P< 0.01). Allele's frequencies for alleles (A) and (G) were 0.53 and 0.47 respectively according to the analysis of transferrin gene (Tf). High correlation was found between polymorphism and three genotypes, namely, AACC, AGCT and GGTT by two alleles AC (A), as a wild and GT as a mutant allele respectively were observed. Homogenotype in A14037G SNP (AG) AG was superior to other genotypes (AA and GG) in all traits except for fat percentage.

Study Design. A case-control study was performed on 105 patients with idiopathic scoliosis (IS) and 210 unrelated gender-matched controls from Bulgarian population. Objective. Investigation of the association between common genetic... more

- by Alexandre Loukanov and +1
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- Genetic Polymorphisms

Introduction: Many genes have been associated with risk of primary hip osteoarthritis. Recently, a special attention has been focused on asporin (ASPN) encoding gene, an extracellular cartilaginous matrix protein in relationship with TGF-beta pathway, known to have a negative regulator role in chondrogenesis. Several polymorphic variants (D8-D19) of the gene with aspartic acid (D) codon repeats have been described. D14 allele was found to be the most common in hip and knee osteoarthritis in Japanese populations; the presence of D14 allele was also associated with increased radiological severity of the disease. Subsequent
researches have showed an increased D14 allele frequency for male patients with primary hip osteoarthritis in the UK population, but this association has not been found in Spanish population. The purpose
of the present study was to assess the association of ASPN polymorphisms with primary hip osteoarthritis in Romanian population.
Material and methods: ASPN D-repeat polymorphisms were identified by genotyping 50 patients with primary hip osteoarthritis and 50 control
subjects. The combination of alleles identified in the two groups was examined. In the patient group, identified alleles were associated with radiographic severity of osteoarthritis. Results: Seven alleles were identified (D12-D18), D13 allele being the most frequent in both groups,
followed by D15 and D14 alleles respectively. We found a statistically significant association of D13 allele frequency in men control group (p=0.02), while the D14 allele was found with a significantly higher
frequency in men with hip osteoarthritis (p=0.005), and low frequency in women (p=0.02). D14 allele was associated with increased radiological severity in both sexes, while D13 allele was associated with decreased
radiological severity in women. Conclusions: Our data show that D14 allele is associated with the risk of hip osteoarthritis in Romanian
men and is a protective allele for women. D13 allele confers protection against hip osteoarthritis in men and is associated with decreased radiological severity in women. D14 allele is associated with increased
radiological severity in both sexes.

- by Iulia Lupan
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- Genetic Polymorphisms, Genetic determinism, hip osteoarthritis, asporin

Although the involvement of genetic abnormalities in autism spectrum disorders (ASD) is well-accepted, recent studies point to an equal contribution by environmental factors, particularly environmental toxicants. However, these toxicant-related studies in ASD have not been systematically reviewed to date. Therefore, we compiled publications investigating potential associations between environmental toxicants and ASD and arranged these publications into the following three categories: (a) studies examining estimated toxicant exposures in the environment during the preconceptional, gestational and early childhood periods; (b) studies investigating biomarkers of toxicants; and (c) studies examining potential genetic susceptibilities to toxicants. A literature search of nine electronic scientific databases through November 2013 was performed. In the first category examining ASD risk and estimated toxicant exposures in the environment, the majority of studies (34/37; 92%) reported an ass...

- by Stephen Genuis
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- Autism, Toxicology, Heavy metals, Humans

We investigated systolic dysfunction by the use of biochemical laboratory tests and perfusion single-photon emission computed tomography imaging in 32 Pakistani subjects exhibiting symptoms of this disorder. To investigate underlying genetic causes, such as familial hypercholesterolemia, DNA samples from these subjects were screened by PCR-SSCP and DNA sequencing to detect changes in the low density lipoprotein receptor gene (LDLR). A novel mutation (1171G>A) in exon 8 and two polymorphisms (1167G>A and 1413 A>G) in exons 8 and 10 of the LDLR gene were found. In silico tools such as SIFT, PolyPhen-2, KD4v, and Project HOPE were used to predict the effect of this mutation on protein structure and function.

- by Nadeem A Kizilbash
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- Genetic Polymorphisms, PET and SPECT imaging

Catalase (CAT) plays a central role in the protection of different cell types against the deleterious
effects of hydrogen peroxide. In human, CAT is implicated in many physiological and pathological
conditions including idiopathic male infertility. In this study we examined the association between
CAT levels in seminal plasma with different sperm parameters and with CAT–262 C/T polymorphism
and their risk for idiopathic male infertility in Algeria. Semen and blood samples were
obtained from 111 infertile males and 104 fertile controls from the region of Eastern Algeria
following informed consent. Standard semen parameters, DNA integrity, and CAT concentration in
seminal plasma were evaluated. CAT-262C/T genotypes were screened using allele specific PCR.
Seminal CAT activity was significantly different (p<0.0001) between infertile males and controls, it
was also markedly decreased in oligo-astheno-teratozoospermia (p<0.0001), azoospermia
(p<0.0001), and normozoospermia (p=0.045) subgroups compared to controls. Positive correlations
between CAT activity and semen parameters (volume, motility, concentration, and morphology)
were detected, but not with sperm DNA integrity. There was no direct association between
CAT-262C/T polymorphism and general male infertility. However, the results presented in this
study showed that CAT activity is remarkably associated with the CAT-262T allele (p=0.001) and
the different CAT-262C/T genotypes. This study highlighted the major differences in the seminal
plasma CAT content between infertile and fertile males and the differences of CAT concentration
between different CAT-262C/T genotypes carriers.

- by nourelhouda bousnane
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- Oxidative Stress, Antioxidants, Genetic Polymorphisms, Catalase

Objetivo: Diante do consenso científico de que a lesão perirradicular é de etiologia microbiana, questionamentos têm sido levantados acerca da influência de outros fatores como, polimorfismo genético, na sua prevalência, severidade e resposta ao tratamento. A proposta deste estudo foi investigar a influência do polimorfismo genético do gene do CD14 no sucesso e fracasso do tratamento endodôntico em indivíduos brasileiros.
Métodos: A população estudada foi composta por 42 pacientes com dentes apresentando lesão perirradicular pós-tratamento e 41 pacientes com dentes apresentando canal tratado e saúde perirradicular (controle). Amostras de saliva dos pacientes foram coletadas, o DNA foi extraído e o polimorfismo genético do gene do CD14 (-206 T/T) foi avaliado pelo método molecular da Reação em Cadeia da Polimerase (PCR).
Resultados: Nenhuma diferença estatisticamente significativa foi observada entre os genótipos CC, CT e TT e os alelos C e T polimórficos (p>0.05) no sucesso/fracasso do tratamento endodôntico. Na análise bivariada entre o tratamento endodôntico e as covariáveis, o polimorfismo do CD14 e raça não demonstraram associação significativa com o prognóstico do tratamento endodôntico, enquanto que para gênero (p=0,047) e tabagismo (p=0,020) foi observada associação direta e significativa. Com relação ao gênero, foi demonstrado que o fracasso no tratamento endodôntico é quase três vezes maior nos homens quando comparado com as mulheres. No caso do tabagismo, o fracasso é quatro vezes maior em pacientes fumantes do que em não fumantes.
Conclusão: O presente estudo sugere que não há associação do polimorfismo do gene do CD14 com o resultado do tratamento endodôntico. Tabagismo, também considerado como modificador de doença, foi significativamente associado com o fracasso endodôntico.

- by Jacques Elion
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- Thalassemia, Molecular Genetics, Genetic Polymorphisms
- by Jacques Elion and +1
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- Infectious Diseases, Genetic Polymorphisms, Sickle Cell Disease

Objective: To investigate whether different genotypes of p.Arg16Gly, p.Gln27Glu, p.Arg19Cys and p.Thr164Ile variants interfere in response to treatment in children and adolescents with moderate to severe acute asthma. Methods: This sample comprised patients aged 2 to 17 years with a history of at least two wheezing episodes and current moderate to severe asthma exacerbation. All patients received multiple doses of albuterol and ipratropium bromide delivered via pressurized metered-dose inhaler with holding chamber and systemic corticosteroids. Hospital admission was defined as the primary outcome. Secondary outcomes were changes in forced expiratory volume in the first second after 1 hour of treatment, and for outpatients, length of stay in the emergency room. Variants were genotyped by sequencing. Results: A total of 60 patients were evaluated. Hospital admission rates were significantly higher in carriers of the genotype AA relative to those with genotype AG or GG, within the p.Arg16Gly variant (p=0.03, test χ 2 , alpha=0.05). Secondary outcomes did not differ between genotypes. Conclusion: Hospital admission rates were significantly higher among carriers of the genotype AA within the p.Arg16Gly variant.

Animal geneticists' unvarying endeavor to maximize profit from livestock can be achieved by improving the genetic potential using appropriate selection methods. Genetic selection is an important tool for gaining maximum benefit from livestock. The improved reproductive efficiency and increased fertility rate of animal will ultimately pave the way for economic benefit of farmers. However, improvement of reproductive traits through selection is usually difficult to accomplish due to low heritability of traits. Therefore, immense efforts are being made to search some of major genes that would influence fecundity of animal. In this present context we focus on various SNPs of prolific genes associated with prolificacy in goat.

- by sidharth prasad mishra and +1
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- Fertility, Genetic Polymorphisms, Goats, Fecundity

Aim: The aim of the present study was to analyze the association between vitamin D receptor (VDR) (rs10735810) gene polymorphism and chronic periodontitis (CP). Methods: A total of 100 subjects were recruited for this study, which included 50 CP and 50 healthy controls. Genomic DNA was extracted from the whole blood collected from the subjects. DNA was amplified using specific primers flanking the FokI region of the VDR gene (rs10735810). The amplicon was further subjected to genotyping using restriction fragment length polymorphism (RFLP) using the FokI enzyme. The genotype obtained based on RFLP pattern was recorded and used for statistical analysis. The distribution of genotypes and allele frequencies in the chronic periodontitis and control groups were compared using the χ2‐test. Results: The CP group displayed the highest frequency of CT (20%) and TT (6%) genotypes when compared with the control subjects. Allele frequency was found to be similar in both groups. The C allele was found to be predominant in the study population compared with the T allele. Conclusion: The present study denotes that the VDR polymorphism (rs10735810) is not associated with CP in the study group analyzed.

- by Karthikeyan Murthykumar and +1
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- Genetics, Vitamin D, Single Nucleotide Polymorphisms (SNPs), Genetic Polymorphisms

Results of population genetic study among eastern Khants from a collection of biological material of
ecological genetics lab. RCMG were presented. On a wide range of biochemical-genetic markers (HP, TF,
GC, PI, ACP, PGM1, GLO1, ESD) and autosomal DNA polymorphisms (CHIT1, ABCC11,NOS3 ) among
Khantian population of Yugan and Agan rivers drainage-basins were analyzed. The gene pool of eastern
Khants includes characters peculiar to both for eastern Eurasian and western Eurasian populations. One of
the main objectives of our work was establishment of the ethnic anthropological importance «new» autosomal
DNA polymorphisms. High degree of CHIT1 polymorphism efficiency in the anthropological relation was
established. The share of western Eurasian genetic component in studied Khantian group forms 43.3% and
eastern Eurasian proportion was 56.7%. Our data about serological and biochemical genetic markers (AB0,
MN, RH, TF, GC, C’3, PI, ACP, PGM1, ESD, GLO1) allows to estimate genetic relationship between Khants
and neighboring and more remote Finno-Ugric and

- by Nailya Spitsyna and +1
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- Human Genetics, Genetic Polymorphisms, Human Population Genetics, DNA markers

—The aim of the study was to evaluate the association between the angiotensin-converting enzyme ACE I/D (rs 4340) polymorphism and DNA damage in patients with essential hypertension (EH). The I/D polymorphism of ACE was determined by polymerase chain reaction in 170 male hypertensive patients and 64 normotensive blood donors. We used flow cytometry to determine the levels of cell death, micronuclei and accumulation of peripheral blood leukocytes in G1/G0, S, G2/M phases of the cell cycle. Additionally, the whole blood samples were incubated in vitro at 4°C for 24 h to investigate the genotype effects on the susceptibility of cells to DNA damage. We found lower frequency of cells in DNA synthesis S phase and higher levels of micronuclei in the hypertensive compared to normotensive group (p < 0.05); increased formation of micro-nuclei was seen due to elevated micronuclei frequencies in patients with the ACE II genotype (p < 0.05), but not in ID or DD genotype carriers. Incubation of whole blood samples of normotensive individuals lead to the most active cell death (p < 0.05) and micronuclei formation (p > 0.05) in the II genotype carriers too. However, hypertensive patients displayed different cellular response to incubation-induced DNA damages in the ACE I/D genotype groups; after incubation, the frequencies of micronuclei were significantly higher in the DD genotype carriers (p < 0.05). To conclude, the study suggests that the ACE I/D polymorphism may contribute to mechanisms and intensity of DNA damages in hypertensive and normotensive individuals.

- by Olena Pavlyushchik
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- DNA damage, Hypertension, Genetic Polymorphisms

The frequency of methylenetetrahydrofolate dehydrogenase (MTHFD1) 1958G>A polymorphism was determined using
restriction fragment length polymorphism polymerase chain reaction analysis in a sample of 491 individuals from different
regions of Jordan. The distribution of polymorphic alleles of MTHFD1 1958G>A in the Jordanian population were 65.2% for the
G allele and 34.9% for the A allele. The genotype distributions were 48.7%, 32.8% and 18.5% for the GG, GA and AA genotypes
respectively. Statistical analysis showed no significant correlation between the rates of alleles and genotypes across the
different regions of Jordan. The association of MTHFD1 1958G>A polymorphism with the development of neural tube defects
(NTDs) was examined for 17 mothers from the northern part of Jordan who gave birth to an NTD-affected child during the
period of this study. The results showed no association between these 3 examined polymorphisms and maternal risk for an
NTD-affected child

- by Cansu Çam
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- Genetic Polymorphisms, Behcet's Disease, NFkB
- by Rogerio Rita
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- Autism, Toxicology, Heavy metals, Genetic Polymorphisms
- by Jacques Elion and +1
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- Sickle Cell Anemia, Genetic Polymorphisms, Genetic Susceptibility to Infectious Diseases

"Allele and genotype frequencies for 13 autosomal STR loci included in the Promega Powerplex 16 kit were assessed in 174 individuals from three Garifuna communities of the Caribbean coasts of Honduras (Central America). For the 13 loci the observed heterozygocity frequencies ranged from 0.571 for the D5S818 locus to 0.939 for the D18S51 locus, both in the Corozal population. Deviations from Hardy–Weinberg equilibrium, as well as pairs of loci in linkage disequilibrium (even after Bonferroni corrections of the level of statistical significance) and high Fis values were observed. These ‘‘spurious’’ results are probably caused by population substructure (Wahlund effect within communities) and high endogamy.
©2008 Elsevier Ireland Ltd. All rights reserved."

In the recent original research published on International Journal of Fertility and Sterility the association between tumor necrosis factor-alpha (TNF-α) genetic polymorphisms and endometriosis in 150 Iranian patients suffered this disease. The authors notably found a lower frequency of TNF-α-863C/A allele A among the affected patients in comparison with healthy women, although this difference was not significant by adjusting multiple testing. We deem that the authors should specify, if these patients had peritoneal nodules, ovarian endometrioma/deep infiltrating endo-metriosis (DIE) nodules or combination of them, since it has been hypothesized that these phenotypes may represent three distinct pathogenetic entities of endometriosis.

We evaluated the effect of estrogen receptor (ER)-a and ER-b genes polymorphisms on development of prostate cancer (PCa) and its correlation with serum reproductive hormones and with clinicopathological characteristics in a sample of Iranian men. One hundred sixty-two men with PCa (mean age 63.7 AE 13.4 years) and 324 age-matched healthy controls (mean age 63.1 AE 13.2 years) were recruited in this study. Genotypes for ERa and ER-b genes poly-morphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum levels of reproductive hormones were also measured. Of PCa patients, 38.3%, and 61.7% had localized and advanced tumor, and 45.7%, and 54.3%, had low grade and high-grade cancer, respectively. There was a significant difference in genotype frequency distribution of ERa gene polymorphism (P ¼ 0.002), and ER-b gene polymorphism (P ¼ 0.003) between cancer patients and controls. The ERa Pvull C allele carriers (TC or CC) had a significantly increased risk of PCa compared with the TT homozygotes [odds ratio (OR) 3.12; 95% confidence interval (CI) 1.87-5.84, and OR ¼ 4.73, 95% CI:2.44-7.33, respectively]. It was also found that the ERa XbaI AG (OR ¼ 4.36; 95% CI:2.47-6.68; P ¼ 0.001) and ER-b AluI AG (OR ¼ 2.66, 95% CI:1.61-4.16; P ¼ 0.004) genotypes were significantly associated with increased risk of PCa. The ER-b RsaI genotype was not associated with PCa. Baseline serum free E2 levels tended to be lower in men with PCa (0.35 AE 0.04 pg/ml) compared to healthy men (0.48 AE 0.05 pg/ml). Genotypes which confer susceptibility for developing PCa, accompanied with lowest serum levels of free E2. In the Iranian population, genetic polymorphisms of the ERa and ER-b genes may be involved in the etiology of PCa. ß

- by Mohammad Reza Safarinejad
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- Urology, Prostate Cancer, Estrogen Receptor, Genetic Polymorphisms

Insulin-like growth factors (IGF) regulate growth and development and enhance cellular proliferation. IGF-binding protein-3 (IGFBP-3) inhibits IGF action by competitively binding IGFs that prevents their binding to the IGF cell surface receptor. Altered expression and serum levels of IGFBP-3 are associated with a number of malignancies. Study addressing the effect of IGFBP-3 gene polymorphism on bladder cancer is lacking. The aim of this study was to examine the effect of -202 A/C polymorphism of IGFBP-3 gene on development of bladder transitional cell carcinoma (TCC) and its correlation with serum concentration of IGF-1 and IGFBP-3 and with clinicopathological characteristics. One single nucleotide polymorphism (rs2854744) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) technique. One hundred and sixty-two bladder cancer patients were genotyped for this SNP. The genotypes were compared with those of a random sample of 324 age-matched controls of the general population. Serum levels of IGF-I and IGFBP-3 were also determined. We found statistically significant differences in the genotypic distribution between the cases and the control subject (χ(2) = 6.43, df = 2.0, P = 0.028). Using CC genotype as a reference, the odds ratio for the subjects with AC genotype was 1.76 (95% CI: 1.27-2.84; P = 0.038). We detected a significantly decreased risk of bladder cancer associated with the AA genotype (adjusted OR = 0.48; 95% CI = 0.24-0.64; P = 0.001) compared with the CC genotype. This decreased risk was more pronounced for invasive bladder cancer. Age-adjusted mean serum IGFBP-3 levels were lowest in the individuals with the CC genotype. We found a positive correlation between age-adjusted serum IGFBP-3 levels and circulating IGF-1 concentrations (16% difference in IGFBP-3 in top vs. bottom tertiles of IGF-1, P for trend = 0.001), which was comparable across genotypes at the -202 IGFBP-3 locus (interaction term, F = 0.10, P = 0.87). Genetic polymorphism of the IGFBP-3 gene may be involved in the etiology of bladder TCC, and our results need further confirmation by larger studies.

- by Mohammad Reza Safarinejad
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- Genetics, Urology, Bladder Cancer, Genetic Polymorphisms

We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different ethnicity are required to confirm our findings.

- by Mohammad Reza Safarinejad
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- Genetics, Risk, Bladder Cancer, Genetic Polymorphisms

Apical membrane antigen-1 (AMA-1) and Duffy binding protein (DBP) of plasmodium vivax are potential vaccine candidate antigens. High degree of polymorphism in the candidate antigens may compromise the efficacy of an otherwise effective vaccine. Polymorphic regions of the genes encoding plasmodium vivax. AMA-1 and DBP were analyzed by PCR-RFLP in 25 north Indian isolates of plasmodium vivax. No size variation was seen in target segments of both the genes by PCR. Further analysis of PCR products of AMA-1 and DBP by RFLP using Pvu-II and Eco R-1 endonucleases respectively, also failed to detect polymorphism in both the genes. The presence of low or no variation within these genes may be due to the functional constraints as both the proteins have important functions in the life cycle of the parasite.

- by Umar F A R O O Q Gaur
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- Bioengineering, Bioinformatics, Immunology, Molecular Biology

Introduction. Vitamin D receptor (VDR) gene is recognized as
candidate gene for susceptibility to Type 2 diabetes mellitus
(T2DM). The aim of this study was to investigate the association
between VDR gene polymorphisms and T2DM in Moroccans
patients. Materials and Methods. 176 clinically diagnosed T2DM
patients and 177 healthy controls from the Moroccans population
were recruited. BsmI(rs1544410), FokI(rs10735810) and ApaI
(rs7975232) single nucleotide polymorphisms (SNPS) of the
VDR gene were determined using polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP). A
Vitamin D level was determined using ELISA. Results. The
prevalence of Vitamin D deficiency and insufficiency is
significantly higher in patients with T2DM than in the control
subjects. There was a strong association between fok1
polymorphisms with T2DM (OR = 0,35, 95% CI = 0.14–
0.83, P = 0.018), while the VDR BsmI and ApaI polymorphisms
are not. The Fok1 polymorphism was significantly associated
with increased levels of total cholesterol, LDL cholesterol, HDL
cholesterol and triglycerides (all P values <0.05). We found
significantly elevated systolic blood pressure (P = 0.042) in
association with Apa1. Conclusions. Our study indicated that
vitamin D deficiency was prevalent in Moroccans patients with
T2DM, and each variants in VDR polymorphism may be
associated with different mechanisms that enhance the plasma
lipid profil and the risk of cardiovascular disease. However, the
allele FokI f appears to have protective effect against diabetes.

- by IJSRP Journal
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- Diabetes, Vitamin D, Vitamin D receptor, Genetic Polymorphisms
- by Emőke Endreffy
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- Genetics, Molecular Biology, Chronic kidney disease, Medicine
- by Ligia P Oliveira
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- Medicine, Genetic Polymorphisms

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

- by Mohammad Reza Safarinejad
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- Genetics, Iran, Humans, Medical Oncology

The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34-5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54-4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73-19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34-21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68-18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76-14.72) genotype variant. This study suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1 may be associated with bladder cancer susceptibility in the Iranian population. Further confirmation in large population-based studies is needed.

intravaginal ejaculatory latency time (IELT), and International Index of Erectile Function (IIEF). The efficacy of treatment was assessed using responses to IIEF, and geometric mean IELT evaluation. 5-HTTLPR was genotyped using polymerase chain reaction techniques. A repeated-measures analysis of variance of geometric mean IELT was done to test a genotype effect on treatment outcome with SSRI (sertraline). RESULTS Of 227 participants who completed the study, 175 (77.1%) responded to sertraline (IELT > 1 min). Overall the patients had a 3.7-fold (95% confidence interval, CI, 1.72-5.46) increase of the geometric mean IELT (P = 0.001). The results showed that responses were significantly better for the L A /L A genotype of the 5-HTTLPR polymorphism than for S-allele carriers (P = 0.001). The STin2 12/12 genotype was found more often in those responding to sertraline than in those not responding (P = 0.001). The probability of patients responding sufficiently to sertraline with an L A /L A genotype was highest (odds ratio 4.66, 95% CI, 2.48-6.14). CONCLUSIONS These findings indicate that the genotype of 5-HTT contributes in unique ways to the variation in the outcome of PE treatment with SSRIs.

Background and Aims. The methylenetetrahydrofolate reductase (MTHFR) gene plays a key role in the metabolism of folate and homocysteine (Hcy) and its mutations have been associated with high serum Hcy level. Elevated serum Hcy has been linked to impaired endothelial function and occlusive vascular disease. We studied the association among the different genotypes of all three MTHFR polymorphisms (C677T, A1298C, and G1793A) and the risk of early-onset vasculogenic erectile dysfunction (VED). Methods. We performed a case-control study of 114 men with early-onset VED and 228 age-matched controls. Genotyping of MTHFR gene polymorphisms was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. We also measured plasma lipids, Hcy, folate, and vitamin B12 levels. Results. Patients with early-onset VED had higher serum Hcy levels (12.29 AE 2.32 vs. 9.82 AE 2.35 mmol/L, p 5 0.001) and higher prevalence of 677TT homozygocity compared to controls (15.8% vs. 11.4%, p 5 0.01). Serum Hcy concentration was significantly higher in individuals with 677TT, 1298CC, and 1793GG genotypes. Subgroup analysis according to severity of ED (mild, moderate, and severe) showed that patients with severe VED had higher serum Hcy levels compared to patients with mild VED (13.48 AE 2.51 vs. 11.21 AE 2.32 mmol/L, p 5 0.001). Conclusions. Odds ratio seems to demonstrate that individuals with the MTHFR 677TT genotype and the 677TT þ 1298AC combined genotype had a 3.16-and 3.89-fold increased risk for developing VED, suggesting a possible association of MTHFR poly-morphisms with the risk of early-onset VED. Ó

Objective: To investigate the association between G-protein b3 (GNB3) subunit gene 825C/T polymorphism and vasculogenic ED (VED). Design: Case-control study. Setting: Private urology and andrology clinic. Patient(s): The study included 246 patients with VED and 492 healthy controls, Caucasians of Iranian descent. Intervention(s): Typing of the polymorphism was performed using the polymerase chain reaction restriction fragment length polymor-phism technique. Main Outcome Measure(s): To test the hypothesis of whether the presence of the 825T allele of the GNB3 gene is associated with an increased risk of VED. Result(s): The CT genotype was more prevalent in VED patients relative to healthy controls (adjusted odds ratio [OR] ¼ 2.34; 95% confidence interval [CI], 1.10-4.26). Interaction between T allele carriership and VED was significant. The dominant model CT þ TT variant was associated with a 3.74-fold increase in the adjusted risk (OR ¼ 3.74; 95% CI, 1.11-12.4) for the occurrence of VED. Our results indicate that the GNB3 polymorphism is associated with higher systolic blood pressure, higher dyslipidemia, and higher body mass index. The 825TT genotype was associated with a more than five-fold increased risk of severe VED compared with the 825CC genotype (OR ¼ 5.62; 95% CI, 3.54-9.25). Significantly different onset of age of VED was not found between the genotypes for the GNB3 polymorphism. Conclusion(s): The GNB3 polymorphism is an independent risk factor for VED in Iranian males. Our findings confirm a role of GNB3 in the genetic susceptibility of VED and suggest that GNB3 polymorphism should be taken into consideration to improve the assessment of an individual's risk of VED. (Fertil Steril Ò 2013;99:69-75.

- by Mohammad Reza Safarinejad
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- Urology, Andrology, Erectile dysfunction, Genetic Polymorphisms

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 12.4 years) and 340 age-matched healthy controls (mean age 64.9 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) 3.62, 95% confidence interval (CI): 1.89-7.74, P 0.002), high grade tumor (OR 2.46, 95% CI:1.78-4.72; P 0.006), and advanced disease (OR 4.67, 95% CI: 2.648.61; P 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b "a" variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR 2.12, 95% CI: 1.68-3.44; P 0.031 for 4a/b ab genotype, and OR 4.32, 95% CI: 2.21-6.08; P 0.001 for 4a/b aa genotype). In addition, genotypes with the "a" allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR 4.76, 95% CI: 2.74-8.62; P 0.001) and advanced CaP (OR 5.28, 95% CI: 3.64-8.72; P 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR 0.44, 95% CI: 0.33-0.77; P 0.004, and OR 0.39, 95% CI: 0.26-0.61; P 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.

- by Mohammad Reza Safarinejad
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- Urology, Prostate Cancer, Genetic Polymorphisms, Clinical oncology

Objective: To explore the correlation between apolipoprotein E genetic polymorphism and serum lipid levels. Methods: The genechips method was adopted to detect the ApoE genotype in people undergoing physical examination.The serum lipid levels were compared among the populations with different ApoE genotypes. Results: The ApoE gene showed the polymorphic distribution in populations,in which the distribution frequency of E3 allele was highest,the population containing E2 allele had higher triglyceride level in serum, the population containing E4 allele had higher total cholesterol level in serum. Conclusion: The ApoE gene presents the polymorphic distribution in populations. The E2 allele is correlated with serum high triglyceride level. The E4 allele correlated with serum high total cholesterol level.

- by Fortune Journals
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- Genetic Polymorphisms