急性冠状动脉综合征患者同型半胱氨酸与亚甲基四氢叶酸还原酶基因多态性及其与冠心病其它危险因素的相关分析

The Correlation Analysis of Total Homocysteine Level and Methylene Tetrahydrofolate Reductase Gene Polymorphism With Other Risk Factors in Patients of Acute Coronary Syndrome

目的:探讨急性冠状动脉综合征(ACS)患者同型半胱氨酸(tHcy)与亚甲基四氢叶酸还原酶(MTHFR)基因多态性及其与冠心病其它危险因素的相关性。方法 :连续入选2012-07至2012-12我院收治的ACS患者248例,记录ACS患者的性别、年龄、高血压、糖尿病、吸烟病史,测定其血tHcy、血脂水平及MTHFR基因多态性分布。根据tHcy的四分位点患者分为tHcy≥21.35μmol/L组(A组)、16μmol/L≤tHcy<21.35μmol/L组(B组)、12.68μmol/L≤tHcy<16μmol/L组(C组)、tHcy<12.68μmol/L组(D组)。另选同期健康体检者30例作为tHcy的正常对照。统计分析MTHFR基因多态性及上述危险因素对tHcy的影响及其相关性。结果:248例ACS患者MTHFRC677TTT型分布频率为38%,高tHc(y≥10μmol/L)者达93%,tHcy均值为20.55μmol/L,高于正常者的(8.83±3.54)μmol/L(P<0.05)。A组、B组患者的MTHFRC677T突变基因分布型(CT+TT)比例一致(98.3%和93.6%,P=0.37),显著高于C组和D组(80.3%和64.5%,P<0.01)。A组MTHFR C677T多态性分布TT型比例显著高于B组、C组和D组(67.7%、36.5%、26.2%、24.2%,P<0.01),不同性别、年龄、血脂水平、是否合并糖尿病、高血压各组及吸烟组TT基因型患者tHcy均显著高于CC基因型患者,差异有统计学意义(P<0.01)。多元回归分析显示MTHFR、LDL-C对血浆tHcy存在显著性影响,MTHFR与吸烟之间可能存在交互作用(P<0.05)。结论:ACS患者tHcy显著升高,MTHFRC677 T TT突变是主要决定因素。冠脉传统危险因素中,LDL-C也是tHcy升高的重要影响因素,吸烟与MTHFR存在交互作用。

Objective： To explore the correlation of total homocysteine （tHcy） level and methylene tetrahydrofolate reductase （MTHFR） gene polymorphism with other risk factors in patients of acute coronary syndrome （ACS）. Methods： A total of 248 ACS patients admitted in our hospital from July to December 2012 were studied. The patient＇s gender, age, history of hypertension, diabetes and smoking were recorded, plasma tHcy level, blood lipids and MTHFR gene polymorphism were examined. According to tHey quartiles, the patients were divided into 4 groups, Group A, （tHey--〉 21.35） lamoi/L, Group B, （16 tHey〈21.35）μmol/L, Group C, （12.68 〈 tHcy〈16） μmol/L and Group D, （tHey〈12.68）μmol/L. Meanwhile, 30 healthy subjects were enrolled as Control group. The impact of MTI-IFR genotype polymorphism and the related risk factors on tHey level were statistically analyzed. Results： In ACS patients, the MTHFR C677T TY distribution frequency was 38%, there were 231/248 （93%） of patients had hyper-homocysteinemia as （tHcy I〉 10） tunol/L which was much higher than the normal average level of tHcy（8.83 ± 3.54） umol/L, P〈0.05. In Group A and Group B, the MTHFR C677T mutation gene pattern ratio （CT＋Tr） was statistically the same, 98.3% vs 93.6%, P= 0.37 which was much higher than that in Group C and Group D, 80.3% vs. 64.5%, P〈0.01. The ratio of MTHFR C677T ＂IT distribution in group A was significantly higher than that in groups B, C, and D as 67.7%, 36.5%, 26.2% and 24.2%, P〈0.01 respectively. Plasma tHcy level in ACS patients with MTHFR C677T TI＂ pattern was higher than that withCC pattern, P〈0.01. Multivariate regression analysis displayed that tHcy level was significantly impacted by MTHFR and LDL-C; there might be an interaction between MTHFR and smoking. Conclusion： Plasma tHcy level obviously increased in ACS patients, the MTHFRC 677TTT mutation may play an important role, LDL-C and smoking should also be involve in tHcy elevation.