Investigation of the relationship between MTHFR, IRS and CALCA gene polymorphisms and development of diabetic nephropathy in patients with type 2 diabetes mellitus (original) (raw)
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Diabetes/Metabolism Research and Reviews, 2007
Background Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C>T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy.
Genetics of Type 2 Diabetes- A Review Article
Iranian Journal of Diabetes and Obesity, 2015
ype 2 diabetes (T2D) is a worldwide concern. Based on International Diabetes Federation, 285 million adults aged 20–79 years suffered from diabetes in 2010. About 60% of them located in Asia. Almost 80% of people with diabetes live in developing countries. Around 95% of diabetic patients suffer from T2D (1-3).Worryingly, new findings show decrease in the onset age of T2D. The disease is more frequently reported among young Africans and Pima Indians (4). T2D in Asia differs from the other world regions; since it has developed in younger age group, and in people with much lower bodyT 1. Department of Genetics, Faculty of Medicine, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 2. Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 3. Clinical and Research center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 4. Diabetes Research Center, Shahid ...
MTHFR gene at rs A1298C polymorphism in type II diabetes among Iranian population
Electronic Journal of General Medicine, 2018
Introduction: Diabetes mellitus type II is a complex endocrine and metabolic disorder. Correspondingly, interference between multiple environmental, genetic and epigenetic factors cause a progressive and heterogeneous disorder with varying degrees of insulin resistance and dysfunction of islets. In this account, MTHFR gene (Methylene tetrahydrofolate reductase) is located on the chromosome 1 and its relationship with diabetes is unclear. Methods: In a case-control study, blood samples of 150 patients with type II diabetes referred to the Central Laboratory in Yazd city, Iran was tested to determine the polymorphism A1298C of MTHFR gene using 4P-ARMS-PCR method as the control group 150 normal subjects without diabetes were compared. Results: AA Genotype was reported % 66.4 in patients and 42% in the control group. AC genotype was % 66.30 in patients and % 33.9 in controls. Finally CC genotype was report % 66.64 inpatients and % 66.48in the control group. Our study showed that the prevalence of polymorphisms studied in patients had a significant difference with controlled group (p = 0.000). When checking diabetes complications, there was significant difference between these polymorphisms and neuropathy (p = 0.008). Conclusion: MTHFR gene could be raised as one of the genes associated with susceptibility to type II diabetes. A1298C polymorphism of this gene can also be considered for the incidence of neuropathy.
Journal of the Renin-Angiotensin-Aldosterone System, 2012
Background: Genetic variations have been proposed to play a role in the susceptibility to diabetic nephropathy. Objectives: To check for the association of genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE) genes with the development of diabetic nephropathy among type 2 diabetic patients. Methods: Participants comprised 202 patients with type 2 diabetes, of whom 102 were affected with diabetic nephropathy. Genetic variants corresponding to MTHFR C677T, A1298C and ACE I/D genotypes were determined using the PCR technique coupled with digestion and restriction analysis. Results: Cases with diabetic nephropathy had a significantly higher frequency of the MTHFR 677 TT, 677 CT, ACE DD mutant genotypes compared with diabetic cases without nephropathy. Analysis of the association of studied MTHFR C677T, A1298C and ACE I/D polymorphisms with albuminuria showed that the MTHFR 677 T polymorphism, in the recessive and dominant models, was a risk factor for both micro and macroalbuminuria, while the ACE DD mutant genotype was a risk factor for microalbuminuria and the MTHFR 1298C in the dominant model only was a risk factor for macroalbuminuria. Conclusion: These findings indicate that ACE and MTHFR genetic polymorphisms might be considered as genetic risk factors for diabetic nephropathy among patients with type 2 diabetes.
Diabetes Research and Clinical Practice, 2004
Family-based studies and segregation analyses suggest that inherited factors play a significant role in susceptibility to diabetic nephropathy (DN). Moczulski et al. [Diabetes 47 (1998[Diabetes 47 ( ) 1164[Diabetes 47 ( -1169 found a susceptibility locus for DN in type 1 diabetes covering a 20 cM region on chromosome 3q, with a peak of linkage close to the angiotensin II type 1 receptor (AT1) gene. We examined eight polymorphic markers (D3S1512, D3S1550, D3S1557, D3S1744, D3S2326, D3S3599, D3S3694, and a (CA) n dinucleotide repeat polymorphism in the 3 flanking region of the AT1 gene) spanning about 6.2 megabases (Mb) in the region of maximal linkage with DN on chromosome 3q23-q24. The markers were used to genotype a total of 381 Russian type 1 diabetic subjects, 195 of whom had DN and 186 had no clinical nephropathy. Four of the markers tested, D3S1512, D3S1550, D3S2326, and D3S3599, showed an association with DN in type 1 diabetes mellitus. These markers are located within a 1.0 Mb interval that starts about 4.4 Mb centromeric to the AT1 gene. Thus, our results suggest the existence of the DN susceptibility locus previously described by Moczulski et al. on chromosome 3q.
PLoS ONE, 2013
Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p,5.5E204) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E208) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR),1.38 increased to OR = 2.44, (95%CI = 1.67-3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.
Evaluation of VDR Gene Polymorphisms with Nephropathy Stages in Men with Type 2 Diabetes Mellitus
To appraise the association of VDR FokI and TaqI polymorphisms with diabetic nephropathy patients, a total of 60 men with type 2 diabetes mellitus (T2DM) were enrolled in the recent paper, as well as 17 healthy men as a control. The patients have been divided according to the albumin/creatinine ratio (Normo albuminuria, micro-albuminuria, and macro-albuminuria,). ARMS PCR was used to diagnose the genotypes and allele frequencies of FokI "rs10735810*" and TaqI "rs731236*". The results indicated that FF, Ff and TT, Tt genotype were significantly higher in patients with T2DM than the control (OD=3.375, p=0.001), (OD=4.333, p=0.001), (OD=4.222, p=0.001), and (OD=2.833, p=0.025) respectively. Moreover, the results showed a notable increase of FF, Ff, and TT, Tt genotypes in the patients with micro-albuminuria and macro-albuminuria when compared with patients of normo albuminuria, (p=0.002), (p=0.005), (p=0.001), (p=0.010) respectively. The current outcomes propose that the F allele of FokI and T allele of TaqI polymorphisms in the VDR gene are associated with a higher risk of T2DM and nephropathy stages. Futhermore, the FokI and TaqI can be used as vital markers to predict the risk of complications of diabetes mellitus especially nephropathy.
The association between type 2 diabetes mellitus and A1/A2 polymorphism of glycoprotein IIIa gene
Acta Diabetologica, 2007
Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder caused by a complex interaction of genetic and environmental variables. T2DM is associated with transcription factor 7-like 2 (TCF7L2) and fat mass and obesityassociated (FTO) genetic polymorphism. Objectives: The goal of this study was to examine the common genetic risk factors of T2DM and related metabolic traits in Upper Egyptian population, in attempt to understand the genetic structure of T2DM in the Egyptian community. Methods and Materials: This case control study included 250 participants, 124 T2DM patients and 126 non-diabetics. Using mutagenically separated polymerase chain reaction (MS-PCR), genotyping of single nucleotide polymorphisms (SNP) rs7903146 of TCF7L2 and rs17817449 of FTO genes was carried out. Results: T allele of TCF7L2 variant rs7903146 confers a risk for T2DM (allelic OR=1.97, 95% CI: (1.34 to 2.88) p =<0.001). The minor G allele of FTO rs17817449 polymorphism was significantly higher in diabetics than controls (allelic OR=1.87, 95% CI=1.30 to 2.68, p<0.001). Genotype risk was evident under both recessive and dominant modes of inheritance (OR=3.18, CI (1.35-7.45), P =0.008, OR= 2.04, CI (1.23-3.38), p=0.006) for TCF7L2 and (OR= 2.55, CI (1.28-5.09), p=0.008 and OR= 2.14, CI (1.25-3.63), p= 0.005) for FTO respectively Conclusion: TCF7L2 rs7903146 and FTO rs17817449 variant conferred risk for T2DM in Upper Egyptian population. The study noted the interaction between certain biological and environmental risk factors including BMI, age, and sex and the conferred genetic risk.
Biochemical Profile and Genetic Polymorphism of MTHFRC677T in Risk of Type 2 Diabetes Mellituss
2017
Diabetes mellitus (DM) is a common endocrine metabolic disorder and a leading cause of death worldwide Diabetes type-2 is a multicausal disease which develops slowly and in a stepwise order. Our study showed there was no significant difference in serum high density lipoprotein (HDL) and Tri glyceride (TG) of patients and controls (0.90±0.59 vs 1.15±0.39 p>0.05) and (1.19±0.70 vs 1.01±0.52 p>0.060) respectively. Low density lipoprotein (LDL) and total cholesterol (TC) are significantly higher in patients than control group (4.09±1.14 vs 3.01±1.02 p<0.0002) and (4.21±1.28 vs 3.78±1.29 p<0.05). However, HDL/TC ratio is significantly higher in patients than controls (0.21±0.91 vs 0.30±0.99 p<0.05). Serum levels of all liver enzymes (ALT, AST, and ALP) analyzed are significantly higher in patients than controls (12.69±10.80 vs 4.95±2.66, p<0.0002), (15.99±10.70 vs 6.95±3.84, p<0.0002) and 68.29±27.78 vs 21.27±7.77, p<0.0001) respectively. On genetic level the role...