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目的探讨甲硫氨酸合成酶还原酶(Methionine Synthase Reductase,MTRR)基因多态性对口服叶酸治疗高同型半胱氨酸血症(Hyperhomocysteinemia,HHcy)效果的影响以及基因与环境因素在治疗效果中的交互作用。方法采用前瞻性研究方法,选择河南某医院住院的HHcy病人(Hcy≥15μmol/L)纳入研究队列,给予口服叶酸(5 mg/d)治疗3个月,根据其治疗后的Hcy水平分为干预成功组和失败组。运用Mass Array技术对MTRR基因的2个位点(rs1801394、rs162036)进行基因分型,多因素降维模型(MDR)分析基因-环境交互作用。结果 rs1801394突变杂合型AG(OR=3.07,95%CI:1.82~5.18)、突变纯合型GG(OR=4.50,95%CI:1.32~15.35)、突变基因型(AG+GG)(OR=3.20,95%CI:1.93~5.31)和等位基因G(OR=2.43,95%CI:1.62~3.66)能增加叶酸治疗HHcy失败的风险。rs162036突变杂合型AG(OR=0.44,95%CI:0.25~0.78)、突变基因型(AG+GG)(OR=0.45,95%CI:0.26~0.77)和等位基因G(OR=0.51,95%CI:0.32~0.82)能降低治疗失败的风险。基因与环境交互作用分析结果显示rs1801394与冠心病病史存在交互作用(OR=5.08,95%CI:2.97~8.68)。结论 MTRR基因上rs1801394位点和rs162036位点可对口服叶酸降HHcy的效果产生影响,rs1801394位点和冠心病病史对叶酸降HHcy效果的影响具有交互作用。
Objective To investigate the effect of methionine synthase reductase (MTRR) gene polymorphism on the effect of oral folic acid on hyperhomocysteinemia (HHcy) and the effect of genetic and environmental factors on the therapeutic effect Interaction. Methods A prospective study was conducted to select HHcy patients (Hcy≥15μmol / L) hospitalized in a hospital in Henan Province for inclusion in the study cohort. Oral folic acid (5 mg / d) was given for 3 months. According to the Hcy level after treatment, Success and failure groups. Mass Array was used to genotype the two loci of MTRR gene (rs1801394, rs162036), and to analyze the gene-environment interaction by multivariate dimensionality reduction model (MDR). Results The rs1801394 mutant heterozygous AG (OR = 3.07, 95% CI: 1.82-5.18), the homozygous mutant GG (OR = 4.50,95% CI: 1.32-15.35) = 3.20, 95% CI: 1.93-5.31) and allele G (OR = 2.43, 95% CI: 1.62-3.66) increased the risk of failure of folic acid in the treatment of HHcy. rs162036 mutant heterozygous AG (OR = 0.44, 95% CI: 0.25-0.78), mutant genotypes (ORG = 0.45,95% CI: 0.26-0.77) and allele G , 95% CI: 0.32 to 0.82) reduced the risk of treatment failure. The interaction between gene and environment showed that rs1801394 interacted with the history of coronary heart disease (OR = 5.08, 95% CI: 2.97-8.68). Conclusion The rs1801394 and rs162036 sites on MTRR gene may affect the effect of oral administration of folic acid on HHcy. The rs1801394 site and the history of coronary heart disease have an interaction effect on the HHcy folic acid.