The MTHFR C677T polymorphism is associated with mitral valve rheumatic heart disease

OBJECTIVE: Rheumatic heart disease (RHD) is a serious complication of rheumatic fever (RF). Plasma homocysteine (Hcy) levels are increased in RHD patients. MTHFR catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate and plays a vital role in Hcy metabolism. We hypothesize that the MTHFR C677T polymorphism is associated with a risk of RHD. PATIENTS AND METHODS: Eighty-six patients with RHD and 130 matched controls without a history of RHD were eligible for the study. The diagnosis of RHD was made according to modified Jones' criteria and echocardiography. Using echocardiography, RHD patients were further divided into mitral valve lesion (MVL) and combined valve lesion (CVL) groups. MTHFR C677T polymorphisms were genotyped by DNA sequencing. The chi-squared test was used to evaluate differences in genotypes. RESULTS: Control genotypes were in Hardy-Weinberg equilibrium. The C677T homozygous genotype (OR = 4.09; 95% CIs 1.16-14.44; p = 0.020) and recessive model (TT vs. CC+CT; OR = 4.05; 95% CIs 1.17-14.04; p = 0.019) were significantly associated with MVL RHD. CONCLUSIONS: This is the first study to investigate the association between the MTHFR C677T polymorphism and risk of RHD. The MTHFR C677T polymorphism is associated with RHD in patients with MVLs, perhaps via an Hcy-mediated cytokine effect.