轻中度高血压患者中MTHFR C677T与血清叶酸水平变化的相关性研究

Association test of MTHFR C677T genotype and the changes of serum folic acid level in mild-to-moderate hypertensive patients

目的探讨轻中度高血压患者亚甲基四氢叶酸还原酶(MTHFR)C677T多态性位点与血清叶酸水平变化间的关系。方法从哈尔滨、沈阳、北京、西安、上海、南京6城市收集的480位28～75岁轻中度原发性高血压患者,按1∶1∶1的原则随机分为3组;对照组、0.4mg叶酸组、0.8mg叶酸组每日分别服用10mg马来酸依那普利、10mg马来酸依那普利+0.4mg叶酸、10mg马来酸依那普利+0.8mg叶酸,连续服用8周。收集治疗前后的血清叶酸水平、MTHFRC677T位点的基因型及其他相关指标。本研究对主要资料完整者371人(男156人,女215人)的MTHFRC677T位点与血清叶酸水平变化间的关系进行统计分析。结果①对照组中C677T基因型对叶酸变化水平无明显作用,各基因型间的差异均无统计学意义。②试验组中血清叶酸变化水平在C677TCC、CT和TT基因型间的变化趋势基本一致,TT型增加水平最少,CC型增加最多。以677CC基因型人群的叶酸变化水平为参照,合并叶酸组中TT基因型在调整前(β=3.99,P=0.034)后(β=5.68,P<0.001)差异均有统计学意义;0.4mg叶酸组和0.8mg叶酸组TT基因型在调整前(β分别为5.33和2.64,P分别为0.061和0.280)差异无统计学意义,调整后(β分别为5.60和4.68,P分别为0.031和0.050)差异有统计学意义。各组中CT基因型调整前后的差异均无统计学意义(P>0.05)。结论轻中度高血压患者中MTHFRC677T的基因型对叶酸的疗效具有一定的作用。

Objective To test association of changes of serum folic acid level with MTHFR C677T genotype in the mild-to-moderate hypertensive patients. Methods A total of 480 eligible patients with essential hypertension, aged 28-75, from Harbin, Shenyang, Beijing, Xi＇an, Shanghai and Nanjing were recruited, and randomly divided into three groups separately with different drug combination treatments, for consecutive 8 weeks, where 10 mg enalapril treatment group defined as the control group, and combined with different daily dose of 0.4 mg or 0.8 mg folic acid as the trials. In this present study, major variables containing pre-and post-treatment serum folic acid, and MTHFR C677T genotypic data were collected. Then we chose of them 371 individuals （male 156 vs female 215） with completing information and further analyzed for the inter-relationships of changes of serum folic acid level with MTHFR C677T genetype by general statistical methods （i. e. t-test, ANOVA, and multivariate regression models）. Results （1） There was no association of changes of serum folic acid level with C677T genetype. （2）The changes of the serum folic acid level was the highest in the individuals with CC genotype of C677T and the lowest in those with TT genotype and the middle in those with CT genotype in the trial groups. Compared with the changes of serum folic acid level of individuals with 677 CC genotype, that of those with TT genotype was significantly different in the total trial groups; and is also significantly different after adjusted, but no significantly difference before adjusted for sex, age, BMI and so on in the 0.4 mg and 0.8 mg trial groups. There was no significant difference of the changes of serum folic acid level between the individuals with heterozygous CT genotype and those with homozygous CC genotype in all groups. Conclusions MTHFR C677T polymorphisms can moderately modify therapeutic effect of the folic acid in the mild-to-moderate hypertensive patients.