载脂蛋白E-CI-CII基因多态性与冠状动脉粥样硬化性心脏病易感性的关系  

The apolipoprotein E-CI-CII gene cluster polymorphisms and coronary artery disease

作　　者：汪春红[1] 周新[2] 郑芳[2] 韩定芬[1] 施群[1] 刘芳[2] 

机构地区：[1]武汉大学医学院卫生学教研室,430071 [2]中南医院基因诊断中心

出　　处：《中华医学遗传学杂志》2005年第2期164-168,共5页Chinese Journal of Medical Genetics

基　　金：湖北省教育厅攻关基金(2000B03012);武汉大学医学院杰出青年基金(2003)~~

摘　　要：目的　探讨载脂蛋白E- CI- CII基因簇多态性与冠状动脉粥样硬化性心脏病(冠心病)的关系。方法　采用多重扩增突变系统(multiplex amplification refractory mutation system ,multi- ARMS)和聚合酶链反应-限制性片段长度多态性法检测了2 0 3例患者和36 5名对照的apo E、CI、CII基因多态性;L INKAGE程序计算连锁不平衡系数D和D′。结果　病例组apo E基因E3/4基因型频率为0 .2 5 9、ε4等位基因型频率为0 .139,均高于对照组,差异有统计学意义(P<0 .0 5 ) ;apo C 基因H2等位基因型频率在病例组为0 .2 0 5 ,高于对照组的0 .113,差异有统计学意义(P<0 .0 5 ) ;apo CII基因多态性分布在两组间差异无统计学意义(P>0 .0 5 ) ;apo E、CI基因存在显著的连锁不平衡(D′=0 .6 72 ,P<0 .0 1) ,病例组ε4 - H2 - T1单倍型频率为5 .4 %高于对照组的0 .5 % ,差异有统计学意义(P<0 .0 5 )。调整混杂因素后,ε4、H2等位基因同时携带者吸烟呈显著的相乘交互作用,危险度(odds ratio,OR)及其95 %可信限(95 % confidenceinterval,95 % CI)为18. 3(2 .35～15 0 .81,P<0 .0 5 ) ,交互作用归因比(attributable proportions ofinteraction,API)为5 7.3% ;ε4、H2和多量饮酒三者间呈超相加作用,OR(95 % CI)为12 .7(2 .75 7～5 8.5Objective To investigate associations between the apolipoprotein E-CI-CII gene (apoE-CI-CII) cluster polymorphisms and coronary artery disease (CAD). Methods apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the polymorphisms of both apoCI and apoCII genes were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 203 cases of CAD and 365 controls. Pairwise linkage disequilibrium coefficients (D, D′) were estimated by the LINKAGE program. Results The frequencies of apoE E3/4 genotype (0.259) and ε4(0.139) in CAD group were significantly higher than that in control group(0 125,0.069), ( P <0.05). The significant difference was also found for the apoCI locus, the frequencies of H2 allele were 0.205 in the CAD and 0.113 in the control. Linkage disequilibrium coefficient D′ was 0 672 ( P <0.01) between apoE and apoCI genes. Significant differences for a deficit of ε3-H1-T1 and excess of ε4-H2-T1 were found in the CAD by estimation of the haplotype frequencies. After adjustment for possible confounding factors, the multivariate logistic analysis showed a significant interaction among ε4,H2 and smoking, OR value was 18.3 (95%CI:2.35-150.81, P <0.05),attributable proportions of interaction (API) was 57.3%, it was a multiplicative model. An additive model was shown among ε4, H2 and bibulosity; the odds ratio(OR) (95%CI) and API of their interaction were 12.7(2.8-58.6, P <0.05) and 43.5%, respectively. Conclusion The results suggested that both apoE and apoCI on chromosome 19 were the susceptibility loci for CAD, their linkage disequilibrium should be responsible for the development of CAD. Smoking and bibulosity can significantly increase the risk of CAD.

关 键 词：冠状动脉粥样硬化性心脏病 聚合酶链反应-限制性片段长度多态性法 载脂蛋白E 易感性 interval 连锁不平衡 基因型频率 基因多态性分布 system APOE基因 H2等位基因 95%可信限 交互作用 apoCI 单倍型频率 ratio 冠心病患者 

分 类 号：R541.4[医药卫生—心血管疾病] R543.6[医药卫生—内科学]