BHMT rs3733890基因多态性与叶酸治疗河南汉族HHcy患者效果的前瞻性队列研究

BHMT gene rs3733890 polymorphism and the efficacy of oral folate therapy for Henan Han population with hyperhomocysteinemia:a prospective cohort study

目的:探讨甜菜碱同型半胱氨酸甲基转移酶(BHMT)rs3733890基因多态性与叶酸治疗高同型半胱氨酸血症(HHcy)效果的关联,并分析基因-环境交互作用对疗效的影响。方法:使用前瞻性队列研究,收集2014年7月至12月郑州大学第五附属医院收治的1071例HHcy患者,对其采血并检测血浆同型半胱氨酸(Hcy)水平,随后进行90 d的口服叶酸(5 mg/d)干预治疗。治疗结束时复查血浆Hcy水平,根据复查结果将患者分入治疗成功组(Hcy≤15μmol/L)和治疗失败组(Hcy>15μmol/L)。通过MassArray平台对BHMT rs3733890进行基因分型。运用基于logistic回归的分层分析探究基因-环境的交互作用。结果:①rs3733890基因型在两组间的分布差异有统计学意义(P<0.05)。②携带突变基因型(GA+AA)和突变等位基因(A)的患者,叶酸治疗失败的风险明显升高(P<0.05)。③突变基因型与不良生活习惯(吸烟、饮酒)和既往史(糖尿病、高血压、冠心病)分别存在交互作用。结论:BHMT rs3733890基因多态性与叶酸干预治疗河南汉族HHcy的疗效存在关联,该位点与环境因素的交互作用会影响叶酸治疗效果。

Aim:To investigate the association between BHMT gene rs3733890 polymorphism and the efficacy of oral folate therapy for patients with hyperhomocysteinemia(HHcy)and analyze the effects of gene-environment interactions on the efficacy of therapy.Methods:We utilized a prospective cohort study among the Chinese Han population.All HHcy participants were outpatients treated at the Fifth Affiliated Hospital of Zhengzhou University from July to December 2014.Blood samples were collected from 1071 eligible patients at baseline,and these individuals received folate treatment(5 mg/d)for 90 days.A total of 638 patients included in the final analysis were grouped into the treatment success group[homocysteine(Hcy)≤15μmol/L]and the treatment failure group(Hcy>15μmol/L)based on post-treatment Hcy levels.Time-of-flight mass spectrometry(MassArray system)was used to assess the genotype of BHMT rs3733890.The stratified analysis was used to explore potential gene-environmental interactions based on logistic regression.Results:The genotype distribution presented distinct differences between the two groups(P<0.05).The patients with mutant genotype(GA+AA)and allele(A)had increased risk of treatment failure(P<0.05).Furthermore,synergistic effects of BHMT rs3733890 polymorphism with smoking,drinking as well as previous history on the efficacy of oral folate therapy were also found.Conclusion:The polymorphism of BHMT rs3733890 is strongly associated with the efficacy of oral folate therapy in Henan Han population with HHcy.The combinations of genetic mutations of BHMT rs3733890 and undesirable environmental factors could directly influence the efficacy of folate treatment for HHcy.