新疆维吾尔族人群血红素加氧酶-1基因启动子区多态性与心肌梗死的相关性

Association between genetic polymorphism in the promoter region of heme oxygenase- 1 and myocardial infarction in patients from Uighur ethnics of Xinjiang Autonomous Region

目的探讨新疆维吾尔族人群血红素加氧酶-1（HO-1）启动子区（GT）n重复序列多态性与心肌梗死的相关性。方法选择2006年1月至2008年6月在新疆医科大学第一附属医院急救中心急诊入院并行经皮冠状动脉造影检查确诊的维族心肌梗死患者287例（A／VII组）；对照组190例，为同期入院行冠状动脉造影排除冠心病者，体格检查及胸片、标准12导联心电图、肝胆B超、血尿便常规均未见异常。各组间性别、年龄等一般资料经统计学检验差异无统计学意义，具有可比性。以上两组入选对象如合并心力衰竭、肝功能异常、胆囊疾病、多脏器功能衰竭、全身免疫系统性疾病、血液系统疾病、感染等疾病之一者均予以排除。血生化检测指标包括血总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、血清胆红素。采用聚合酶链反应．非变性聚丙烯酰胺凝胶电泳方法检测HO-1启动子区（GT）n重复序列多态性，同时进行血清胆红素含量测定。用Hardy-Weinberg平衡检验样本群体代表性；各组基因型和等位基因频率差异比较用X^2检验；综合评价各因素与心肌梗死相关性采用多因素Logistic回归分析；以P〈0．05为差异具有统计学意义。结果心梗组体重指数、甘油三酯、高密度脂蛋白胆固醇及合并高血压的比例较对照组明显拜高（P〈0．01）。血红素加氧酶-1基因型分布在心梗组和对照组70值分别为2．09和0．05（P〉0．05），符合Hardy-Weinberg平衡检验，具群体代表性。AMI组和对照组L／L基因型频率（35．5％）及L型等位基因频率（57．8％）分布差异具统计学意义（X^2=11．65，P=0．001；70=11．32，P=0．003）；L／L基因型胆红素水平较S／S、L／S基因型明显下降（P〈0．01）。Logistic回归分析结果显示体重指数、高血压、甘油三酯、血胆红素及HO-1基因多态性是心肌梗死发生的危险因素。结论对于新疆维吾尔族人群，HO-1启动子区（GT）17,重复序列多态性与心肌梗死的发生具有相关性；L等位基因可增加心肌梗死发生的风险，可能和该基因多态性所导致的血清胆红素水平降低有关。

Objective To investigate the association between acute myocardial infarction （AMI） and the （GT） n repeat sequence polymorphism in promoter region of heine oxygenase-1 （HO-1）, and to study the influence of serum bilirubin on AMI as well for HO-1 as a rate-limiting enzyme of bilirubin production in patients from Uighur national minority. Method Totally 287 patients with AMI evidenced by coronary arteriography admitted from January 2006 to June 2008 were eligible for being studied, and another 190 healthy subjects without anomaly in coronary arteriography, and with normal findings in physical examination and in variety of biochemical assays were enrolled as controls. Serum total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL- C）, low-density lipoprotein cholesterol （LDL-C）, serum bilirubin were detected. Polymerase chain reaction-non- denaturing polyacrylamide gel electrophoresis was used to detect HO-1 promoter （GT）n repeat polymorphism, and at the same time the serum bilirubin was determined. The group representation of samples was tested with Hardy- Weinberg balance test. Differences in distributions of genotypes and alleles between AMI patients and control subjects were analyzed using Chi-square test. Comprehensive evaluation of the factors associated with myocardial infarction using muhi-factor Logistic regression analysis. P 〈 0.05 was considered as significantly different. Results Body mass index, triglyceride, high density lipoprotein cholesterol and the proportion with hypertension in myocardial infarction group was significandy higher than those in control group （P 〈 0.01 ）. The X^2 values of HO-1 genotype distribution in the myocardial infarction group and the control group were 2.09 and 0.05, respectively （ P 〉 0.05）, consist with the results of Hardy-Weinberg balance test. The HO-1 genotype was classified into three groups, L/L, L/S and S/S. The L/L genotype frequency （35.5%） and L-allele frequency （57.8%） in AMI group and in control group showed statistically significant differences, respectively （X^2 = 11.65, P = 0.001;Z2 = 11.32, P = 0.003）. The bilirubin level of L/L genotype significantly decreased compared with that of S/S, L/ S genotype （ P all 〈 0. 1301 ）. Logistic regression analysis showed that body mass index, high blood pressure, triglycerides, blood bilirubin and HO-1 gene polymorphism are risk factors of myocardial infarction. Conclusions To the Xinjiang Uighur ethics, HO-1 promoter （GT）n repeat polymorphism and the occurrence of myocardial infarction are relevant. People with L allele genotype have lower serum bilirubin and higher risk of myocardial infarction.