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    不同剂量叶酸对不同MTHFR C677T基因型的H型高血压病病人的疗效分析

    Efficacy analysis of different doses of folic acid in H-type hypertension patients with different MTHFR C677T genotypes

      摘要
    • 摘要:
      目的： 通过给予不同基因型的H型高血压病病人不同剂量的叶酸补充，观察疗效，以期实现H型高血压病人的精准药物治疗。
      方法： 选择2020年5月至2022年5月安徽省第二人民医院心血管内科经治的H型高血压病病人197例，所有病人均行亚甲基四氢叶酸还原酶（MTHFR）基因C677T位点基因型检测，检测同型半胱氨酸（Hcy）水平和颈动脉内膜中层厚度（IMT），根据不同基因型分为野生型（CC）29例、杂合型（CT）74例和突变型（TT）94例。所有病人根据具体病情选择合适的降压药物单独或联合降压药物治疗，197例病人随机分为A组（服用0.4 mg/d叶酸，）和B组（服用0.8 mg/d叶酸），3个月后观察口服不同剂量叶酸的不同MTHFR C677T基因型H型高血压病治疗效果。
      结果： 经叶酸补充治疗3个月后，3种基因型不同叶酸治疗剂量的病人Hcy均较治疗前有降低低，差别有统计学意义（P ＜ 0.05）。CC型和CT型病人，口服0.4 mg/d叶酸与0.8 mg/d叶酸治疗后比较，Hcy差别无统计学意义（P ＞ 0.05），而TT型病人口服0.8 mg/d叶酸较口服0.4 mg/d叶酸后Hcy水平差异有统计学意义（P ＜ 0.01）。相比IMT正常组，等位基因T的基因频率在异常组MTHFR C677T位点较高（P ＜ 0.01）。logistic逐步回归分析显示颈动脉硬化形成与MTHFR C677T基因突变有相关性，logistic回归方程：LogitP = –2.662 + 0.050X1 + 1.092X2。突变基因T 和Hcy为颈动脉硬化形成的危险因素（P ＜ 0.01）。
      结论： H型高血压病人的叶酸补充治疗是有效的，其中MTHFR C677T CC型和CT型服用0.4 mg/d叶酸补充治疗即可，而MTHFR C677T TT型需服0.8 mg/d才能有较好的临床疗效；突变基因T 和Hcy为颈动脉硬化形成的危险因素，某种程度上可预测颈动脉斑块严重程度。

       

      Abstract:
      Objective To observe the efficacy of folic acid supplementation by giving different doses to patients with different genotypes of H-type hypertension, with the aim of achieving precision drug treatment for this condition.
      Methods 197 patients with H-type hypertension treated in the Department of Cardiology of Anhui No. 2 Provincial People's Hospital between May 2020 and May 2022 were enrolled and tested for methylenetetrahydrofolate reductase (MTHFR) gene C677T locus genotype, homocysteine (Hcy) and intima-media thickness（IMT）. According to different genotypes, they were divided into the wild group (CC group, n = 29), heterozygous group (CT group, n = 74) and the mutant group (TT group, n = 94). All patients received appropriate antihypertensive drugs, either as monotherapy or combination therapy, based on their specific condition. The patients were randomly divided into group A (folic acid 0.4 mg/day) and group B (folic acid 0.8 mg/day). After 3 months, the therapeutic effects were observed among H-type hypertensive patients with different MTHFR C677T genotypes.
      Results After 3 months of folic acid supplementation treatment, the levels of Hcy in patients with different folic acid doses of three genotypes were significantly lower than those before (P ＜ 0.05). In patients with the CC and CT genotypes, there was no significant difference in Hcy levels between the 0.4 mg/d and 0.8 mg/d folic acid groups (P ＞ 0.05), while in patients with the TT genotype, there was a statistically significant difference in Hcy levels between the 0.8 mg/d and the 0.4 mg/d folic acid groups (P ＜ 0.01). Compared with the normal IMT group, the gene frequency of allele T at the MTHFR C677T locus was significantly higher in the abnormal IMT group (P ＜ 0.01). Logistic stepwise regression analysis showed that there was a correlation between carotid atherosclerosis and MTHFR C677T gene mutation, with the logistic regression equation: LogitP = –2.662 + 0.050X1 + 1.092X2. Matant gene T and Hcy was risk factors for carotid atherosclerosis (P ＜ 0.01).
      Conclusions Folic acid supplementation is effective in patients with H-type hypertension. Patients with the MTHFR C677TCC or CT genotype may can take 0.4 mg/d of folic acid supplement treatment, while those with the TT genotype need 0.8 mg/d to have better clinical effect. Mutated genes T and Hcy are risk factors for carotid atherosclerosis, and can predict the severity of carotid plaque to some extent.

       

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