Methylenetetrahydrofolate reductase gene polymorphisms in essential hypertension relation: with the development of hypertensive end-stage renal disease.

BACKGROUND: The pathogenesis of hypertensive nephropathy is multifactoral and in addition to BP, other factors contribute to the development of this renal pathology and its progression to end-stage renal disease. These include genetic predisposition and increased pleasure level of homocysteine-intermediate protein catabolism product known to induce kidney injury. The 677C --> T polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated homocysteine level in the general population, and therefore it has been hypothesized to be a risk factor for the development of renal failure in the course of essential hypertension.

METHODS: In this case-control, cross-sectional study the frequency of the MTHFR 677C --> T and the 1298A --> C polymorphism was compared between patients with hypertension-related chronic renal failure (n = 90), patients with essential hypertension without kidney injury (n = 90), and healthy individuals (n = 90) who were matched for age and gender. In addition, the influence of these polymorphisms on homocysteine concentration in individuals with essential hypertension was examined.

RESULTS: The frequency of the MTHFR 677 TT genotype did not differ between groups (4.5%, 12.3%, and 11.1%, respectively). Patients with hypertension and the 677TT genotype showed significantly higher homocysteine levels as compared to individuals having CC and CT. In the multivariate correlation analysis the MTHFR 677TT genotype (P < .01; beta = 0.27), age (P < .001; beta = 0.33), and body mass index (P < .01; beta = 0.3) were independent predictors for total homocysteine level.

CONCLUSIONS: Plasma homocysteine levels in individuals with essential hypertension is affected by the MTHFR 677C --> T polymorphism. However, we did not prove the hypothesis that MTHFR 677C --> T influences the risk of development of renal failure in the course of hypertension.