Differential contribution of MTHFR C677T variant to the risk of diabetic nephropathy in Lebanese and Bahraini Arabs

Abstract

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 C677T and A1298C MTHFR gene variants and altered homocysteine concentrations in Lebanese and Bahraini type 2 diabetes (T2DM) DN patients. 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. C677T and A1298C genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) analysis, and homocysteine was measured by ELISA. A1298C allele and genotype distribution were comparable between DN and DWN patients in both communities. However, there was enrichment of the 677T 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)]. The contribution of C677T single nucleotide polymorphism to increased risk of DN (presumably by increasing homocysteine concentrations) must be evaluated in the context of the ethnic background.