血红素氧化酶1启动子区功能性多态位点与冠心病易感性的关联  

Association of Functional Polymorphisms in Heme Oxygenase-1 Gene Promoter and Susceptibility of Coronary Artery Disease: Evidence from Classification Tree

作　　者：麦瑞琴[1] 张国红[2] 陈宋明[3] 

机构地区：[1]汕头大学医学院第一附属医院检验科,广东省汕头市515041 [2]汕头大学医学院病理教研室,广东省汕头市515041 [3]汕头大学医学院第一附属医院心血管内科,广东省汕头市515041

出　　处：《中国动脉硬化杂志》2014年第3期265-268,共4页Chinese Journal of Arteriosclerosis

基　　金：广东省自然科学基金资助项目(07008215)

摘　　要：目的血红素氧化酶1（HO-1）是诱导型血红素代谢限速酶，具有抗氧化与抗炎作用。该基因启动子区（GT）n重复序列与单核苷酸多态性（SNP）影响HO-1蛋白的表达。本研究探讨HO-1启动子区联合STR-SNP多态性与冠心病易感性间的关联。方法毛细管电泳与Sanger测序分析171例冠心病及70例对照个体HO-1基因启动子区（GT）n重复序列与SNP分型。分类树模型预测多态性对冠心病患者与对照者的辨析能力，多因素Logistic回归分析多态性与冠心病易感性的关联，多因素降维法分析多态性与危险因素间的交互作用。结果STR、SNP标记分类树模型对冠心病患者、对照个体的正确分类比例为71.0％（P〈0.001）。STR-SNP单体型是冠心病独立危险因素（OR：1.890，95％CI：1.162-3.076，P=0.010），与吸烟存在交互作用（P=0.008）。STR-SNP与吸烟交互作用明显增加冠心病患病风险（OR：6.994，95％CI：3.428～14.272，P=0.001）。结论HO-1基因启动子区功能性 STR、SNP可作为冠心病易感风险评估的分子标记。Aim Heme oxygenase 1 （ HO-1 ） is a rate-limiting enzyme in the degradation of heme and has potent anti-oxidant and anti-injury effects. The HO-I gene promoter has different （GT）n repeats （STR） and single nucleotide polymorphisms （SNP） associated with its expression. In this study, we aimed to assess the association between combination of STR and SNP in the HO-1 gene promoter and the susceptibility for coronary heart disease. Methods 171 patients with coronary heart disease and 70 control subjects with sex and age matching were collected ; Capillary electrophoresis and Sanger sequencing were used for genotyping. Classification tree was performed to distinguish patients from controis. Multiple factors regression was employed to detect the association between genotyping and disease susceptibility, and multifactor dimensionality reduction method was used to identify best factor interacting with STR-SNP haplotype. Results The classification tree distinguished patients with coronary heart disease from controls with 71% of correct predic- tion （P 〈 0. 001 ）. STR-SNP haplotype was an independent risk factor for coronary heart disease （ OR： 1. 890, 95 % CI ： 1. 162 - 3. 076, P =0. 010）, and interacted with smoking to increase risk （OR： 6. 994, 95% CI： 3.428 ~ 14. 272, P = 0. 001 ）. Conclusion STR and SNP functional polymorphisms in HO-1 promoter could be a marker for screening sus- ceptibility individual of coronary artery disease.

关 键 词：冠心病 血红素氧化酶1 多态性 易感性 

分 类 号：R5[医药卫生—内科学]