Brehima Diakité - Academia.edu (original) (raw)

Papers by Brehima Diakité

BMC Genetics, Sep 1, 2016

Background: Breast cancer is the most common cause of cancer death among women. Several studies h... more Background: Breast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population. Methods: A case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed. Results: Genotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006). Conclusions: We have noted that the implication of C3435T variant on the risk of breast cancer was ethnicitydependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.

African Health Sciences, Jul 24, 2012

Background: Methylenetetrahydrofolate (MTHFR) enzyme plays an important role in folate metabolism... more Background: Methylenetetrahydrofolate (MTHFR) enzyme plays an important role in folate metabolism which is involved in DNA methylation, repair, and synthesis. Objective: We investigated if the MTHFR C677T polymorphism modulates the risk of developing breast cancer in Moroccan women. Methods: Genotyping was performed by PCR-RFLP method on a sample of 96 patients with breast cancer and 117 controls. Results: A positive correlation was found between the MTHFR C677T polymorphism and progesterone receptors expression (p= 0.04). According to menopausal status, the heterozygous CT (OR = 2.29 and P = 0.03) was statistically significant in pre-menopausal women. There was a significant association between C677T polymorphism and breast cancer risk in both additive (OR = 2.2, 95% CI = 1.24-3.86, p = 0.007) and dominant (OR = 2.10, CI 95% = 1.21-3.64, p = 0.008) models. In addition, the T allele were associated with a high breast cancer risk (OR = 1.59, 95% CI = 1.04-2.44, p = 0.03). Conclusion: In the light of our preliminary study, 677T allele and 677CT MTHFR genotype may represent a genetic determinant increasing breast cancer risk in Moroccan women. A larger study including a larger sample size and more information is needed to confirm our conclusions.

Molecular Biology Reports, Oct 24, 2019

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of... more Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

International Journal of Environmental Research and Public Health

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Afri... more While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger’s test. Twenty-seven articles conducted across seven West Afri...

Genetics Research

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and h... more Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, a...

Pharmacogenetics and Genomics

Objectives The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polym... more Objectives The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study. Patients and methods Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays. Results The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 c...

Medicine, 2021

Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide ra... more Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3...

Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof bre... more Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results : Twenty-one publications with cas...

Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof bre... more Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results : Twenty-one publications with cas...

Background: The effect of the Arg72Pro variant of the P53 gene on the risk of developing breast c... more Background: The effect of the Arg72Pro variant of the P53 gene on the risk of developing breast cancer remains variable in populations. However, using strategies like grouping age-matched controls with disease cases may provide a strong meta-analysis. Our goal was to perform a meta-analysis in order to study the association of Arg72Pro variant of P53 gene and breast cancer. Methods: Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched control studies on breast cancer that evaluated the genotype frequencies of the Arg72Pro P53 gene were selected. Fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the disease risk. Hardy-Weinberg equilibrium test was used to measure deviation in the distribution of genotypes in controls. Inconsistency was calculated to determine heterogeneity among the studies. Estimated publication bias was ...

Gene Reports, 2018

Synergic predisposing effect of G894T (eNOS), 4G/5G (PAI) and T1131C (APOA5) polymorphisms to Myo... more Synergic predisposing effect of G894T (eNOS), 4G/5G (PAI) and T1131C (APOA5) polymorphisms to Myocardial Infarction

Molecular Biology Reports, 2019

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of... more Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% h...

BMC research notes, Jan 21, 2017

Our case-control study aimed to access the potential association of insertion/deletion (I/D) ACE ... more Our case-control study aimed to access the potential association of insertion/deletion (I/D) ACE (angiotensin converting enzyme) gene polymorphism with myocardial infarction (MI) risk of occurrence among a sample of Moroccan patients, especially young ones. Distribution of I/D ACE gene variant among cases vs controls, showed that healthy controls carried out higher frequency of wild type allele I compared to cases (23.5% vs 21.79% respectively), when cases were carrying higher frequency of mutant allele D (78.21% vs 76.5% for controls). Patients were-after this- divided into two groups of < 45 and > 55 years of age, to investigate whether or not younger patients carried out higher frequency of the mutant allele D, than older ones. As expected, < 45 years old patients carried out more DD genotype than older ones (68.9% vs 54.6% respectively), and higher frequency of mutant allele D (81.08% vs 75% respectively). Besides, a tendency to a positive association was found under th...

Biomedical Reports, 2016

Coagulation factor Leiden mutation has been described as a common genetic risk factor for venous ... more Coagulation factor Leiden mutation has been described as a common genetic risk factor for venous thrombosis; however, this mutation was reported to be practically absent in an African population. Recently, a novel nonsense mutation in the gene encoding factor V has been associated with the risk of occurrence of cardio-cerebrovascular diseases such as stroke and venous thrombosis. The aim of the present study was to investigate whether the factor V Leiden (FVL) and C2491T nonsense mutations are associated with the risk of developing myocardial infarction. Genotyping of FVL and C2491T FV was performed using the polymerase chain reaction restriction fragment length polymorphism method on a sample of 100 patients with myocardial infarction as well as 211 controls. In the study population, the frequency of the FVL mutation was practically zero. However, with regard to the C2491T mutation, the TT genotype was associated with an increased risk of myocardial infarction [odds ratio (OR)=3.16, 95% confidence interval (CI): 1.29-7.71, P=0.03]. A significant association between the C2491T FV mutation and the risk of myocardial infarction was identified using recessive (OR=2.74, 95% CI: 1.14-6.58, P=0.04), dominant (OR=1.85, 95% CI: 1.13-3.04, P=0.02) and additive (OR=1.88, 95% CI: 1.25-2.80, P=0.004) models. Furthermore, a positive correlation was found between the presence of the C2491T FV mutation and hypertension (P=0.02), which is associated with myocardial infarction. In conclusion, the results of the present study suggested that the C2491T nonsense mutation of the FV gene may be a risk factor for myocardial infarction in a Moroccan population.

Biomedical Reports, 2016

Myocardial infarction (MI) is a common complex pathology, localized in the main leading causes of... more Myocardial infarction (MI) is a common complex pathology, localized in the main leading causes of mortality worldwide. It is the result of the interaction of genetic and environmental factors. The aim of the present study was to investigate the potential association of C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) (rs1801133) and G20210A factor II prothrombin (FII) (rs1799963) polymorphisms with the susceptibility of MI. Following extraction by the standard salting-out procedure, DNA samples of 100 MI patients and 182 apparently healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism using Hinf I and HindIII restriction enzymes, respectively. The results show a significant association of the G20210T FII polymorphism with the MI risk. The frequencies of the heterozygote genotype GA, homozygous mutated AA and the G20210A allele was higher among patients compared to controls (GA: 59 vs. 5.5%, P<0.001; AA: 10 vs. 0%, P=0.003; and 20210A: 39.5 vs. 2.7%, P<0.003), suggesting that this polymorphism may be a potential genetic marker for MI. No significant association was observed between the C677T MTHFR and MI occurrence, and there was more heterozygote CT in the patient group compared to the controls. As a multifactorial disease, the development of MI may be the result of numerous factors that influence synergistically its occurrence. Thus, further studies are merited to try to better assess these associations (gene-gene and gene-environment interactions).

Journal of Genetics, 2016

Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammato... more Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammatory and thrombotic metabolisms play an important role in the development of ischaemic stroke. The present study aimed to assess the relationship between T1131C APOA5 and SG13S114 ALOX5AP polymorphisms and the risk of ischemic stroke in 175 cases and 201 controls. Genotyping was performed by high resolution melting and polymerase chain reaction restriction fragment length polymorphism methods. In the case of T-1131C APOA5, a modest risk of ischaemic stroke was noticed with CC (OR: 2.86; 95% CI = 1.24-6.58; Pc = 0.039) and C allele (OR: 1.54; 95% CI = 1.01-2.33; Pc = 0.014). For SG13S114 ALOX5AP, a significant association was observed among subjects with TT (OR: 2.57; 95% CI =1.49-4.83; Pc = 0.009) and T allele (OR: 1.59; 95% CI = 1.16-2.19; Pc = 0.008). According to the risk factors of ischaemic stroke, a positive correlation was observed only between SG13S114 variant of ALOX5AP gene and hypertension (Pc = 0.026). Despite lower sample size, T-1131C APOA5 and SG13S114 variants could be considered an independent genetic risk factor of ischaemic stroke in Moroccan population.

International Journal of Innovation and Scientific Research, Aug 2, 2014

In this article, we focus our work on the modeling of genetic risk factors on ischemic strokes oc... more In this article, we focus our work on the modeling of genetic risk factors on ischemic strokes occurred. To do this, MOTS-CLEFS: AVC ischémique, facteurs de risques génétiques, modélisation, régression logistique et Test d'ajustement.

Journal of Genetics, 2015

† GMRAVC, Moroccan group for stroke research. Brehima Diakite and Sellama Nadifi contributed equa... more † GMRAVC, Moroccan group for stroke research. Brehima Diakite and Sellama Nadifi contributed equally to this work.

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 2014

IBD (Crohn's disease and Ulcerative Colitis) is chronic and multifactorial disease of the gas... more IBD (Crohn's disease and Ulcerative Colitis) is chronic and multifactorial disease of the gastrointestinal tract. Till now, his pathogenesis remains unclear. It involves innate immunity, environmental component and genetic predisposition. Polymorphisms in NOD2/CARD15 have been implicated in Crohn's disease in several ethnic groups. The purpose of our study was to assess the frequency of the three major variants of this gene (Leu1007fsinsC, R702W, and G908R) in Moroccan IBD patients and to determine a possible effect of these variants on Disease's phenotype and clinical course. A total of 96 Moroccan unrelated IBD patients and 114 healthy controls were genotyped (PCR-RFLP method) for the three main polymorphisms. In this study, no correlation was found between NOD2/CARD15 polymorphisms and ulcerative colitis or Crohn's disease in our population. Nevertheless, 3020insC (Leu1007fsinsC) variant was associated to a structuring behaviour on CD patients. These findings sugg...

SpringerPlus, 2015

Purpose: The cell-cycle checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular... more Purpose: The cell-cycle checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular responses to DNA damage, whose defects has been associated with increased risk for breast cancer. The CHEK2 1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries. However, the 1100delC mutation has been investigated in different case-control studies and none in Moroccan population. The aim of this study was to evaluate the prevalence of this variant and determine its contribution to the development of breast cancer in sporadic cases and also in members of breast cancer families who tested negative or positive for a deleterious mutation in BRCA1/BRCA2. Methods: In this case-control study we performed the CHEK2 1100delC mutation analysis by ASO-PCR in 134 breast cancer patients and 114 unaffected control individuals. Most of these families had several cases of breast cancer or ovarian cancer (or both). Results: No CHEK2 1100delC mutations were detected in any of 134 individuals, including 59 women diagnosed with breast cancer at an early age (<40 years), 10 women with bilateral breast cancer, and 6 women with ovarian cancer. Conclusion: Our preliminary genetic analysis are consistent with the reported very low frequency of CHEK2 1100delC mutation in North American populations (compared with Northern Europe), rendering CHEK2 1100delC such as an unlikely to be major breast cancer susceptibility genes.

BMC Genetics, Sep 1, 2016

Background: Breast cancer is the most common cause of cancer death among women. Several studies h... more Background: Breast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population. Methods: A case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed. Results: Genotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006). Conclusions: We have noted that the implication of C3435T variant on the risk of breast cancer was ethnicitydependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.

African Health Sciences, Jul 24, 2012

Background: Methylenetetrahydrofolate (MTHFR) enzyme plays an important role in folate metabolism... more Background: Methylenetetrahydrofolate (MTHFR) enzyme plays an important role in folate metabolism which is involved in DNA methylation, repair, and synthesis. Objective: We investigated if the MTHFR C677T polymorphism modulates the risk of developing breast cancer in Moroccan women. Methods: Genotyping was performed by PCR-RFLP method on a sample of 96 patients with breast cancer and 117 controls. Results: A positive correlation was found between the MTHFR C677T polymorphism and progesterone receptors expression (p= 0.04). According to menopausal status, the heterozygous CT (OR = 2.29 and P = 0.03) was statistically significant in pre-menopausal women. There was a significant association between C677T polymorphism and breast cancer risk in both additive (OR = 2.2, 95% CI = 1.24-3.86, p = 0.007) and dominant (OR = 2.10, CI 95% = 1.21-3.64, p = 0.008) models. In addition, the T allele were associated with a high breast cancer risk (OR = 1.59, 95% CI = 1.04-2.44, p = 0.03). Conclusion: In the light of our preliminary study, 677T allele and 677CT MTHFR genotype may represent a genetic determinant increasing breast cancer risk in Moroccan women. A larger study including a larger sample size and more information is needed to confirm our conclusions.

Molecular Biology Reports, Oct 24, 2019

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of... more Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

International Journal of Environmental Research and Public Health

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Afri... more While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger’s test. Twenty-seven articles conducted across seven West Afri...

Genetics Research

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and h... more Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, a...

Pharmacogenetics and Genomics

Objectives The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polym... more Objectives The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study. Patients and methods Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays. Results The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 c...

Medicine, 2021

Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide ra... more Cytochrome P450 enzymes play a central role in the phase I biotransformation process of a wide range of compounds, including xenobiotics, drugs, hormones and vitamins. It is noteworthy that these enzymes are highly polymorphic and, depending on the genetic makeup, an individual may have impaired enzymatic activity. Therefore, the identification of genetic variants in these genes could facilitate the implementation of pharmacogenetic studies and genetic predisposition to multifactorial diseases. We have established the frequencies of CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) alleles and genotypes in 209 healthy Malian subjects using TaqMan drug metabolism genotyping assays for allelic discrimination. Allele frequencies were 37% for CYP2B6 rs3745274; 38% for CYP2B6 rs2279343; and 75% for CYP3A4 rs2740574 respectively. Overall, the frequencies observed in Mali are statistically comparable to those reported across Africa except North Africa. The major haplotypes in CYP2B6 rs3...

Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof bre... more Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results : Twenty-one publications with cas...

Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof bre... more Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results : Twenty-one publications with cas...

Background: The effect of the Arg72Pro variant of the P53 gene on the risk of developing breast c... more Background: The effect of the Arg72Pro variant of the P53 gene on the risk of developing breast cancer remains variable in populations. However, using strategies like grouping age-matched controls with disease cases may provide a strong meta-analysis. Our goal was to perform a meta-analysis in order to study the association of Arg72Pro variant of P53 gene and breast cancer. Methods: Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched control studies on breast cancer that evaluated the genotype frequencies of the Arg72Pro P53 gene were selected. Fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the disease risk. Hardy-Weinberg equilibrium test was used to measure deviation in the distribution of genotypes in controls. Inconsistency was calculated to determine heterogeneity among the studies. Estimated publication bias was ...

Gene Reports, 2018

Synergic predisposing effect of G894T (eNOS), 4G/5G (PAI) and T1131C (APOA5) polymorphisms to Myo... more Synergic predisposing effect of G894T (eNOS), 4G/5G (PAI) and T1131C (APOA5) polymorphisms to Myocardial Infarction

Molecular Biology Reports, 2019

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of... more Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% h...

BMC research notes, Jan 21, 2017

Our case-control study aimed to access the potential association of insertion/deletion (I/D) ACE ... more Our case-control study aimed to access the potential association of insertion/deletion (I/D) ACE (angiotensin converting enzyme) gene polymorphism with myocardial infarction (MI) risk of occurrence among a sample of Moroccan patients, especially young ones. Distribution of I/D ACE gene variant among cases vs controls, showed that healthy controls carried out higher frequency of wild type allele I compared to cases (23.5% vs 21.79% respectively), when cases were carrying higher frequency of mutant allele D (78.21% vs 76.5% for controls). Patients were-after this- divided into two groups of < 45 and > 55 years of age, to investigate whether or not younger patients carried out higher frequency of the mutant allele D, than older ones. As expected, < 45 years old patients carried out more DD genotype than older ones (68.9% vs 54.6% respectively), and higher frequency of mutant allele D (81.08% vs 75% respectively). Besides, a tendency to a positive association was found under th...

Biomedical Reports, 2016

Coagulation factor Leiden mutation has been described as a common genetic risk factor for venous ... more Coagulation factor Leiden mutation has been described as a common genetic risk factor for venous thrombosis; however, this mutation was reported to be practically absent in an African population. Recently, a novel nonsense mutation in the gene encoding factor V has been associated with the risk of occurrence of cardio-cerebrovascular diseases such as stroke and venous thrombosis. The aim of the present study was to investigate whether the factor V Leiden (FVL) and C2491T nonsense mutations are associated with the risk of developing myocardial infarction. Genotyping of FVL and C2491T FV was performed using the polymerase chain reaction restriction fragment length polymorphism method on a sample of 100 patients with myocardial infarction as well as 211 controls. In the study population, the frequency of the FVL mutation was practically zero. However, with regard to the C2491T mutation, the TT genotype was associated with an increased risk of myocardial infarction [odds ratio (OR)=3.16, 95% confidence interval (CI): 1.29-7.71, P=0.03]. A significant association between the C2491T FV mutation and the risk of myocardial infarction was identified using recessive (OR=2.74, 95% CI: 1.14-6.58, P=0.04), dominant (OR=1.85, 95% CI: 1.13-3.04, P=0.02) and additive (OR=1.88, 95% CI: 1.25-2.80, P=0.004) models. Furthermore, a positive correlation was found between the presence of the C2491T FV mutation and hypertension (P=0.02), which is associated with myocardial infarction. In conclusion, the results of the present study suggested that the C2491T nonsense mutation of the FV gene may be a risk factor for myocardial infarction in a Moroccan population.

Biomedical Reports, 2016

Myocardial infarction (MI) is a common complex pathology, localized in the main leading causes of... more Myocardial infarction (MI) is a common complex pathology, localized in the main leading causes of mortality worldwide. It is the result of the interaction of genetic and environmental factors. The aim of the present study was to investigate the potential association of C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) (rs1801133) and G20210A factor II prothrombin (FII) (rs1799963) polymorphisms with the susceptibility of MI. Following extraction by the standard salting-out procedure, DNA samples of 100 MI patients and 182 apparently healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism using Hinf I and HindIII restriction enzymes, respectively. The results show a significant association of the G20210T FII polymorphism with the MI risk. The frequencies of the heterozygote genotype GA, homozygous mutated AA and the G20210A allele was higher among patients compared to controls (GA: 59 vs. 5.5%, P<0.001; AA: 10 vs. 0%, P=0.003; and 20210A: 39.5 vs. 2.7%, P<0.003), suggesting that this polymorphism may be a potential genetic marker for MI. No significant association was observed between the C677T MTHFR and MI occurrence, and there was more heterozygote CT in the patient group compared to the controls. As a multifactorial disease, the development of MI may be the result of numerous factors that influence synergistically its occurrence. Thus, further studies are merited to try to better assess these associations (gene-gene and gene-environment interactions).

Journal of Genetics, 2016

Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammato... more Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammatory and thrombotic metabolisms play an important role in the development of ischaemic stroke. The present study aimed to assess the relationship between T1131C APOA5 and SG13S114 ALOX5AP polymorphisms and the risk of ischemic stroke in 175 cases and 201 controls. Genotyping was performed by high resolution melting and polymerase chain reaction restriction fragment length polymorphism methods. In the case of T-1131C APOA5, a modest risk of ischaemic stroke was noticed with CC (OR: 2.86; 95% CI = 1.24-6.58; Pc = 0.039) and C allele (OR: 1.54; 95% CI = 1.01-2.33; Pc = 0.014). For SG13S114 ALOX5AP, a significant association was observed among subjects with TT (OR: 2.57; 95% CI =1.49-4.83; Pc = 0.009) and T allele (OR: 1.59; 95% CI = 1.16-2.19; Pc = 0.008). According to the risk factors of ischaemic stroke, a positive correlation was observed only between SG13S114 variant of ALOX5AP gene and hypertension (Pc = 0.026). Despite lower sample size, T-1131C APOA5 and SG13S114 variants could be considered an independent genetic risk factor of ischaemic stroke in Moroccan population.

International Journal of Innovation and Scientific Research, Aug 2, 2014

In this article, we focus our work on the modeling of genetic risk factors on ischemic strokes oc... more In this article, we focus our work on the modeling of genetic risk factors on ischemic strokes occurred. To do this, MOTS-CLEFS: AVC ischémique, facteurs de risques génétiques, modélisation, régression logistique et Test d'ajustement.

Journal of Genetics, 2015

† GMRAVC, Moroccan group for stroke research. Brehima Diakite and Sellama Nadifi contributed equa... more † GMRAVC, Moroccan group for stroke research. Brehima Diakite and Sellama Nadifi contributed equally to this work.

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 2014

IBD (Crohn's disease and Ulcerative Colitis) is chronic and multifactorial disease of the gas... more IBD (Crohn's disease and Ulcerative Colitis) is chronic and multifactorial disease of the gastrointestinal tract. Till now, his pathogenesis remains unclear. It involves innate immunity, environmental component and genetic predisposition. Polymorphisms in NOD2/CARD15 have been implicated in Crohn's disease in several ethnic groups. The purpose of our study was to assess the frequency of the three major variants of this gene (Leu1007fsinsC, R702W, and G908R) in Moroccan IBD patients and to determine a possible effect of these variants on Disease's phenotype and clinical course. A total of 96 Moroccan unrelated IBD patients and 114 healthy controls were genotyped (PCR-RFLP method) for the three main polymorphisms. In this study, no correlation was found between NOD2/CARD15 polymorphisms and ulcerative colitis or Crohn's disease in our population. Nevertheless, 3020insC (Leu1007fsinsC) variant was associated to a structuring behaviour on CD patients. These findings sugg...

SpringerPlus, 2015

Purpose: The cell-cycle checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular... more Purpose: The cell-cycle checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular responses to DNA damage, whose defects has been associated with increased risk for breast cancer. The CHEK2 1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries. However, the 1100delC mutation has been investigated in different case-control studies and none in Moroccan population. The aim of this study was to evaluate the prevalence of this variant and determine its contribution to the development of breast cancer in sporadic cases and also in members of breast cancer families who tested negative or positive for a deleterious mutation in BRCA1/BRCA2. Methods: In this case-control study we performed the CHEK2 1100delC mutation analysis by ASO-PCR in 134 breast cancer patients and 114 unaffected control individuals. Most of these families had several cases of breast cancer or ovarian cancer (or both). Results: No CHEK2 1100delC mutations were detected in any of 134 individuals, including 59 women diagnosed with breast cancer at an early age (<40 years), 10 women with bilateral breast cancer, and 6 women with ovarian cancer. Conclusion: Our preliminary genetic analysis are consistent with the reported very low frequency of CHEK2 1100delC mutation in North American populations (compared with Northern Europe), rendering CHEK2 1100delC such as an unlikely to be major breast cancer susceptibility genes.