Differential contribution of MTHFR C 677 T variant to the risk of diabetic nephropathy in Lebanese and Bahraini Arabs

Background: Methylenetetrahydrofolate reductase ( MTHFR ) gene variants and hyperhomocysteinemia have been implicated in the pathogenesis of diabetic nephropathy (DN) in various ethnic groups. We investigated the association of C 677 T and A 1298 C MTHFR gene variants and altered homocysteine concentrations in Lebanese and Bahraini type 2 diabetes (T2DM) DN patients. Methods: Bahraini subjects comprised 224 DN patients and 328 T2DM patients with normal urine albumin [diabetes without nephropathy (DWN)]. Lebanese subjects comprised 252 DN and 309 DWN patients. C 677 T and A 1298 C genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) analysis, and homocysteine was measured by ELISA. Results: A 1298 C allele and genotype distribution were comparable between DN and DWN patients in both communities. However, there was enrichment of the 677 T allele, together with C / T and T / T genotypes in Lebanese but not Bahraini DN patients, thereby conferring DN susceptibility [odds ratio (OR) (95% CI)=2.43 (1.89–3.11) and OR (95% CI)=1.15 (0.83–1.61), respectively; heterogeneity Q=12.53, p=0.0004)]. Conclusions: The contribution of C 677 T single nucleotide polymorphism to increased risk of DN (presumably by increasing homocysteine concentrations) must be evaluated in the context of the ethnic background. Clin Chem Lab Med 2010;48:1091–4.