载脂蛋白E/CI基因簇与冠心病关系的研究

Genetic association of apoE and apoCI gene polymorphisms with coronary heart disease

目的 探讨载脂蛋白(apo)E、apoCI基因簇多态性与人群冠心病的关系。方法 采用病例对照研究,apoE基因多态性检测用multi-ARMS快速分型法,apoCI基因启动子HpaI位点多态性采用聚合酶链反应-限制性片段长度多态性技术,单倍型频率估计采用EH软件包。病例组186例,平均年龄(65.0±10.6)岁;对照组350名,平均年龄(63.6±8.3)岁。结果 病例组apoE基因E4/3基因型(26.9％)和ε4等位基因型(14.5％)频率显著高于对照组(12.6％,7.0％),P<0.05。apoCIHpaI位点病例组H2等位基因频率及携带H2等位基因的基因型频率均显著高于对照组。两基因分布在病例组存在显著的连锁不平衡,P<0.01;病例组ε3-H2(16.0％)、ε4-H1(11.6％)和ε4-H2(3.0％)单倍型频率显著高于对照组(9.4％、6.2％、0.8％);apoE-ε4/apoCI-H2单倍型对冠心病发病的贡献率为9.87％。结论 ε4及H2等位基因连锁能显著增加患冠心病的危险性。

Objective To study the genetic association of apolipoprotein (apo) E and apoCI gene polymorphisms with coronary heart disease(CHD) in China. Methods apoE genotypes were identified by multiplex amplification refractory mutation system(multi-ARMS) and the apoCI promoter polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases with CHD(age: 65.0±10.5 years) and 350 controls (age: 63.6±8.3 years). The haplotype frequencies were estimated. Results The frequencies of apoE E4/3 genotype(26.9%) and ε4(14.5%) in CHD group were significantly higher than that in the control group(12.6%, 7.0%), P<0.05. The significant difference was also found for the apoCI locus and the CHD group showed higher rate of both for the H2 allele and genotypes, carrying this allele. Estimation of the haplotype frequencies indicated that the association between the apoE-CI haplotype and CHD was significantly strong. The apoE-ε4/apoCI-H2 was estimated to be responsible for 9.86% of CHD. Conclusion When the subjects carring both ε4 and H2 alleles, they would have higher risk of suffering from CHD than controls.