Correlations of methylenetetrahydrofolate reductase gene C677T polymorphism with ischemic stroke and hyperuricemia in Chinese Han population in Shandong, China

Abstract

Objective To investigate the correlations of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with ischemic stroke and hyperuricemia in Chinese Han population in Shandong, China. Methods The patients with acute ischemic stroke and age- and sex-matched controls in Chinese Han population in Shandong, China were enrolled. Polymerase chain reaction amplification and microarray hybridization were used to detect the MTHFR gene C677T polymorphism, and the serum uric acid concentration was measured. Results A total of 145 patients with acute ischemic stroke and 145 age-and sex-matched controls in Chinese Han population in Shandong, China were enrolled. The proportion of diabetes (26.90% vs. 6.89%; χ2=20.653, P<0.001) and fasting blood glucose (5.56 ± 1.57 mmol/L vs. 5.01±1.11 mmol/L; t=-3.390, P=0.001), homocysteine (median, interquartile range: 18.2[16.30-22.55 μmol/L] vs. 15.20[12.10-17.85 μmol/L]; Z=-6.323, P<0.001), and uric acid (43.0[361.60-490.45 μmol/L] vs. 285.9[267.00-346.25 μmol/L]; Z=-10.360, P<0.001) levels in the ischemia stroke group were significantly higher than those in the control group. The distribution frequencies of TT genotype (42.07% vs. 15.17%; χ2=25.673, P<0.001) and T allele (58.28% vs. 34.48%; χ2=33.008, P<0.001) in the ischemia stroke group were significantly higher than those in the control group. Multivariate logistic regression analysis showed that the uric acid (odds ratio [OR] 1.018, 95% confidence interval [CI] 1.013-1.024; P<0.001), TT genotype (vs. CT genotype OR 6.774, 95% CI 1.779-25.507; P=0.005), hypertension (OR 1.919, 95% CI 1.013-3.636; P=0.045), and homocysteine (OR 1.153, 95% CI 1.059-1.258; P=0.001) were the independent risk factors for ischemic stroke. The ischemic stroke group was combined with the control group, a total of 101 patients had hyperuricemia, and 189 had normal uric acid. The proportion in patients with diabetes (32.67% vs. 11.64%; χ2=23.749, P<0.001), as well as total cholesterol (5.67±1.56 mmol/L vs. 5.10±1.33 mmol/L; t= -3.255, P<0.001) and homocysteine (19.50[17.10-24.70 μmol/L] vs. 15.40[12.60-18.05 μmol/L]; Z= -7.236, P<0.001) levels in the hyperuricemia group were significantly higher than those in the normal uric acid group. The distribution frequencies of the TT genotype (55.45% vs. 13.76%; χ2=56.409, P<0.001) and T allele (71.9% vs. 32.54%; χ2=79.561, P<0.001) were significantly higher than those in the normal uric acid group. Multivariate logistic regression analysis showed that the TT genotype (vs. CC genotype, OR 6.434, 95% CI 2.334-17.736; P<0.001), CT genotype (vs. CC genotype, OR 2.234, 95% CI 1.019-4.898; P=0.045), homocysteine (OR1.081, 95% CI 1.010-1.157; P=0.024), and total cholesterin (OR 1.363, 95% CI 1.123-1.653; P=0.002) were the independent risk factors for high hyperuricemia. Conclusions MTHFR gene C677T TT genotype and serum uric acid level are the independent risk factors for ischemic stroke in Chinese Han population in Shandong, China. MTHFR gene C677T TT genotype is also an independent risk factor for hyperuricemia in this population. Adjusting dietary habit may have a positive significance for the prevention of ischemic stroke in Chinese Han population in Shandong, China. Key words: Stroke; Brain Ischemia; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Uric Acid; Hyperuricemia; Genetic Predisposition to Disease; Risk Factors; Han Nationality