Differential contribution of MTHFR C677T 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 C677T and A1298C 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. C677T and A1298C genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) analysis, and homocysteine was measured by ELISA. RESULTS: 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)]. CONCLUSIONS: 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.

Incidence and risk factors of hypertension among Saudi type 2 diabetes adult patients: an 11-year prospective randomized study.

AIMS: Insofar as hypertension is a risk factor for cardiovascular morbidity and mortality in Type 2 diabetes mellitus (T2DM), this study investigated the incidence of hypertension and associated risk factors in Saudi T2DM patients. METHODS: A hospital-based, 11-year (1993-2004) prospective study of 916 adult originally normotensive T2DM Saudi patients (488 male and 428 female). T2DM was diagnosed as per World Health Organization (WHO) criteria, while hypertension was assessed according to the Seventh Joint National Criteria for Hypertension Classification (JNVII). Risk factors were analyzed on those who developed hypertension. RESULTS: The hypertension incidence was 17.2/100 person-years, based on 2833.63 person-years of cohort group follow-up. Age-adjusted Cox regression coefficient showed that the significant risk factors for developing hypertension were older age, higher HbA(1c), BMI, elevated triglycerides (>1.8 mmol/l) and creatinine (>115 mmol/l), smoking, proteinuria, microalbuminuria, lack of physical exercise, and retinopathy, while anti-platelet and lipid-lowering drugs had lower hypertension hazard ratios. Cox proportional hazard showed that older age, male gender, higher BMI, diabetes duration (<5 years), and retinopathy were independent predictors of hypertension, while exercise, lipid-lowering, and anti-platelet medications were associated with reduced hypertension incidence rate. CONCLUSIONS: Incidence of hypertension in Saudi T2DM patients is comparable to other communities, with older age, male gender, higher BMI, diabetes duration of <5 years and retinopathy being strong predictors for hypertension development.