BRAP、ADAM8、ITIH3、IL-15、COX-2基因多态性与冠心病的相关性研究

科研成果详情

题名	BRAP、ADAM8、ITIH3、IL-15、COX-2基因多态性与冠心病的相关性研究
其他题名	The association between the genetic polymorphisms of BRAP、ADAM8、ITIH3、IL-15、COX-2 and coronary artery disease
作者	金可可
学位类型	硕士
导师	徐力辛
答辩日期	2012-05-31
学位授予单位	温州医科大学
学位专业	内科学
关键词	冠状动脉粥样硬化性心脏病细胞因子乳腺癌易感基因1相关蛋白单核苷酸多态性基质辅助激光解吸电离飞行时间质谱
摘要	目的研究中国南方汉族人群乳腺癌易感基因1相关蛋白（BRAP）、去整合素-金属蛋白酶8（ADAM8）、中间α胰蛋白酶抑制因子H3（ITIH3）、白介素-15（IL-15）和环氧化酶-2（COX-2）多态性与冠心病的相关性。方法采用病例对照研究，本研究选择于2010年4月至2011年2月在温州医学院附属第一医院心内科住院患者。研究对象分两组：（1）冠心病组，共283例，其中急性心肌梗死68例，陈旧性心肌梗死22例，心绞痛193例。心肌梗塞的诊断符合WHO 1999年诊断标准，心绞痛患者均经冠脉造影证实至少一支冠状动脉直径狭窄≥50%。（2）对照组，包括冠状动脉造影正常及同期心内科住院其他患者(既往无冠心病病史,心电图检查等排除冠心病)共176例。研究对象均无血缘关系，除外炎症、风湿免疫性疾病、肿瘤等全身系统性疾病，但不除外糖尿病、高血压。采用基质辅助激光解吸电离飞行时间质谱技术(matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry，MALDI-TOF-MS)，本研究对459例受试对象的乳腺癌易感基因1相关蛋白（BRCA1 -associatedprotein，BRAP）基因270T>C[2]、BRAP 90A>G[2]、去整合素-金属蛋白酶8( a disintegrin and metalloproteinase 8，ADAM8)基因2662A>C[3]、中间α胰蛋白酶抑制因子H3 (inter-α-trypsin inhibitor H3，ITIH3) 基因108T>C[4]、白介素-15 (interleukin-15，IL-15) 基因13687C>A[5]和环氧化酶-2（cyclooxygenase-2，COX-2）基因8473T>C[6]多态性进行检测，比较不同基因型和等位基因与冠心病患病风险的关系。结果在受检测的5个炎症因子中，BRAP270T＞C及90A＞G多态性在冠心病组与对照组间的差异有统计学意义，其等位基因和基因型的分布频率符合Hardy-Weinberg平衡（分别为：χ2=0.878，P＞0.05；χ2=0.776，P＞0.05）。冠心病组BRAP 270C等位基因和90G等位基因频率高于对照组（分别为：29.5% vs.21.3%，P=0.006；30.0% vs.21.3%，P=0.004），Logistic回归分析发现BRAP 270CC和90GG基因型携带者患冠心病的风险高于BRAP 270TT和90AA基因型携带者（分别为：OR=4.51，95%CI =1.41～14.45，P=0.011；OR=5.09，95%CI =1.60～16.26，P=0.006），且这一关系独立于性别、年龄、吸烟、高血压、糖尿病及血清总胆固醇（total cholestero，TC）、低密度脂蛋白（low density lipoprotein，LDL-C）水平等危险因素之外。没有证据表明其余SNPs与冠心病易感性相关。结论我们的研究显示BRAP基因内含子3 270T＞C和外显子5 90A＞G多态性可能是中国南方汉族人群冠心病发病的遗传危险因素之一。
其他摘要	Objective To investigate the association between the genetic polymorphisms of BRAP、ADAM8、ITIH3、IL-15、COX-2and susceptibility to coronary artery disease (CAD) in south Chinese Han population. Methods　 A case-control study was performed.patients were selected between Apr 2010 and feb 2011 in department of cadiology of the first affiliated hospital of wenzhou medical college.there are two groups in this study:(1) patients with coronary heart disease.A number of 68 patients with acute myocadial infarction,22 patients with old myocadial infarction,193 patients with angina pectoris.The diagnoses of myocadial infarction accord with Standard of Diagnosis of WHO 1999. CHD was defined angiographically as having a≥50% luminal stenosis in at least one of the major epicardial coronary arteries. (2) control group,angiographically normal patients and patients of department of cadiology of the corresponding period.All the subjects have no blood relationship and no inflammatory, rheumatic disease, malignant tumor,while contain diabetes mellitus and hypertension. Using matrix-assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF-MS) method, we analyzed the genotypes and allels of BRCA1 -associatedprotein(BRAP), a disintegrin and metalloproteinase 8(ADAM8), inter-α-trypsin inhibitor H3(ITIH3), interleukin-15(IL-15) and cyclooxygenase-2(COX-2) in 283 CAD patients diagnosed by angiography and 176 healthy controls. To investigate the association between the genetic polymorphisms of five inflammatory factors and susceptibility to coronary artery disease (CAD) in south Chinese Han population.Results 　In these inflammatory factors(BRCA1 -associatedprotein，a disintegrin and metalloproteinase 8，inter-α-trypsin inhibitor H3， interleukin-15，cyclooxygenase-2), the 270T＞C and 90A＞G polymorphisms in the BRAP gene showed a significiant association with coronary artery disease .The allel and genotype frequencies of BRAP gene were consistent with that predicted by Hardy-Weinberg equilibrium (χ2=0.878，P＞0.05；χ2=0.776，P＞0.05,respectively）. The 270C and 90G alleles in CAD patients was significantly higher than that of the control group (29.5% vs.21.3%，P =0.006；30.0% vs.21.3%，P =0.004, respectively). Compared with the genotypes 270TT and 90AA ,270CC and 90GG genotypes had a significantly increased CAD risk with the Logistic regression analysis(OR=4.51，95%CI =1.41～14.45，P=0.011；OR=5.09，95%CI =1.60～16.26，P=0.006, respectively) .This association still existed after adjustment for the sex, age, smoke, hypertension, diabetes,plasma total cholestero and low density lipoprotein levels. No evidence of association was found for other SNPs.Conclusions The 270T＞C and 90A＞G polymorphisms in the BRAP gene might contribute to an increased risk of CAD among south Chinese Han population.
语种	中文
学号	2009010191
发布年限	2010-05-27
毕业论文分类号	0R05
原始专题	第一临床学院
学位论文研究方向	心内科
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全文文件名	2009010191金可可2012内科学.pdf\|2009010191金可可2012内科学.pdf
文献类型	学位论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/119268
专题	温州医科大学
作者单位	溫州医科大学第一临床学院
推荐引用方式 GB/T 7714	金可可. BRAP、ADAM8、ITIH3、IL-15、COX-2基因多态性与冠心病的相关性研究[D]. 温州医科大学,2012.