Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study.
ABSTRACT The role of hyperhomocysteinemia as a risk factor for diabetic long-term complications has not been sufficiently evaluated in prospective studies, considering specific correlates of homocysteine (tHcy) concentration and traditional cardiovascular disease (CVD) risk factors. Fasting tHcy, vitamin B12 and folate plasma levels, the common methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, as well as clinical and lifestyle information were assessed in 216 type 2 diabetic patients attending two outpatient clinics, who had a follow-up evaluation at 65 ± 9 months for the incidence of macroangiopathy. At basal evaluation, mild hyperhomocysteinemia (tHcy ≥ 15 μmol/l) was diagnosed in 21.3% of participants. At follow-up, hyperhomocysteinemia and the distribution of MTHFR C677T genotype did not significantly differ according to the incidence of macroangiopathy. Multiple variables adjusted ORs (95% CI) for CVD associated with mild hyperhomocysteinemia were 1.01 (0.37-2.82); P > 0.05; those associated with MTHFR TT genotype were 0.46 (0.15-1.38); P > 0.05. Although the prevalence of hyperhomocysteinemia was higher in diabetic men (26.9%) than in women (16.1%; P > 0.05), similar results were also observed in a separate sex-analysis. At the multivariate analysis, including in the model other potential CVD risk factors, only creatinine clearance was a significant risk factor for the development of macroangiopathy. In this cohort of diabetic subjects, mild hyperhomocysteinemia and the MTHFR TT genotype are not significant risk factors for the development of macroangiopathy; impaired renal function was confirmed as a significant predictor of this complication.
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ABSTRACT: Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR = 0.78 (95% CI = 0.67-0.92), P = 0.003) and was also associated with 2 h postload plasma glucose (P = 0.04), high-density lipoprotein cholesterol (P = 0.004), and total cholesterol (P = 0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.Experimental Diabetes Research 01/2012; 2012:960318. DOI:10.1155/2012/960318 · 3.54 Impact Factor
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ABSTRACT: Prospective identification of which individuals with diabetes mellitus (DM) are at greatest risk for developing cardiovascular disease (CVD) complications would have considerable public health importance by allowing the allocation of limited resources to be focused on those individuals who would most benefit from aggressive intervention. Over the past 20 years genetic disease association studies have demonstrated that polymorphisms at specific genetic loci may identify those individuals at greatest risk for developing CVD in the setting of DM. This article reviews the evidence accumulated to date on four polymorphic loci with the aim of explaining how these polymorphisms modify the risk for CVD in DM by modifying the functional activity of a specific gene. Use of the knowledge of these genetic differences among individuals in targeting drug therapy (pharmacogenomics) is also discussed.Cardiology clinics 08/2010; 28(3):477-96. DOI:10.1016/j.ccl.2010.04.005 · 1.06 Impact Factor
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ABSTRACT: To find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran. The MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP. The possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p=0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p=0.027, and p=0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p<0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR=4.73, p=0.01). Both MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.Clinical biochemistry 11/2010; 43(16-17):1333-9. DOI:10.1016/j.clinbiochem.2010.08.019 · 2.23 Impact Factor