ST2基因多态性与冠状动脉病变程度关系的研究

Association of ST2 gene polymorphism with angiographic severity of coronary artery disease

目的探讨ST2基因多态性与冠心病患者冠状动脉狭窄程度的相关性。方法采用病例对照研究，选取2008-2012年在武汉协和医院就诊的湖北省汉族人群冠心病患者352例，根据临床情况分为心肌梗死（MI）组和非MI组，并根据冠状动脉造影中累及冠状动脉血管病变情况分组。从Hapmap中挑选ST2信号转导通路中单核苷酸多态性（SNPS）位点，采用Sequenom MassArray和Taqman基因分型技术，分析其在心肌梗死人群中基因型和等位基因频率的分布，并研究其与冠心病人群中冠状动脉病变程度的相关性。结果共9个SNPS位点符合人选条件。其中ST2的核苷酸多态rsl2999364的基因型CC和TT分布频率在冠心病多支病变患者中高于单支病变组（P=0．016），其组合基因型TT＋CT的分布频率在冠心病多支病变患者中低于单支病变人群（P=0．021）。经二元回归校正年龄、性别、吸烟和饮酒、高血压、糖尿病、冠心病家族史、体质指数、三酰甘油、总胆固醇等相关危险因素后，rsl2999364中的基因型CT（OR=0．47，95％CI：0．285-0．778，P=0．003）和TT＋CT（OR=0．555，95％CI：0．347～0．888，P=0．014）是冠心病多支病变的独立保护因素，在MI组中这种保护作用依然独立存在（CT：OR=0．393，95％CI：0．189～0．813，P=0．012；TT＋CT：0R=0．453，95％CI：0．228-0．901，P=0．024）。结论ST2基因多态rsl2999364与冠心病患者冠状动脉病变严重程度有关，是冠心病、心肌梗死患者多支病变的保护因素。

Objective To investigate the relationship between ST2 gene polymorphism and the severity of coronary artery stenosis via angiography. Methods With a case-control design, 352 Hubei Han Chinese patients with coronary heart disease treated at Wuhan Union Hospital from 2008 to 2012 were enrolled in the study. Participants were divided into two groups, the myocardial infarction group and the non-myocardial infarction group, based on clinical data and coronary artery involvement on angiogram. Single Nucleotide Polymor phisms（SNPs） in the ST2 signal transduction pathways chosen from the Hapmap were subjected to analysis using the Sequenom MassArray system and Taqman probes to determine their genotype and allele frequency distribution in myocardial infarction patients and their association with varying degrees of coronary artery involvement in these patients. Results A total of nine SNPs met the inclusion criteria, of which, the frequency distribution of the genotypes TT and CC of the ST2 SNP rs12999364 was higher in the multivessel lesion group than in the single vessel lesion group （P=0. 016）, while the distribution frequency of the combined genotype TT＋CT was lower in the multivessel lesion group than in the single vessel lesion group （P= 0. 021）. With adjustment for traditional risk factors, including age, gender, smoking, drinking, hypertension, diabetes mellitus, family history of CAD, body mass index, triglyceride and total cholesterol, logistic regression analysis showed that genotypes CT and TT＋CT in rs12999364 were independent protective factors for multivessel lesions not only in CAD （CT： OR=O. 471,95 % CI=0.285-0.778, P=0.003;TT＋CT： OR=0.555,95%CI：0.347-0.888, P=0.014）, but also in the myocardial infarction （MI） subgroup （CT： OR=O. 393, 95%CI：0. 189-0. 813, P=0. 0123 TT＋CT： OR=0. 453, 95%CI：0. 228-0. 901, P=0. 024）. Conclusions ST2 gene polymorphism rs12999364 is associated with angiographic severity of coronary heart disease and exhibits protective effects for CAD patients and myocardial infarction patients with multivessel lesions.