摘要
目的探讨三磷酸腺苷结合盒转运子A1(ATP binding cassette transporter 1,ABCA1)基因R219K及M883I单核苷酸多态性(SNP)位点与脂代谢和冠心病(coronary heart disease, CHD)易感性的关系.方法以医院为基础的病例-对照研究.经冠状动脉造影确诊的冠心病病例224例,同一地区正常对照248例.分别以PCR-RFLP和PIRA-PCR对ABCA1第219密码子G→A(Arg219Lys)和第883 G→A(Met883Ile)密码子多态进行检测,比较不同基因型与个体血脂水平和冠心病患病风险的关系.结果吸烟、高血压和高血糖是冠心病的独立危险因素.与携带219RR基因型者比较,携带至少1个219K等位基因者(即RK和KK基因型)冠心病患病风险显著降低59%(OR=0.41, 95% CI=0.27～0.61).而在883位点,II基因型携带者患冠心病率较低(OR=0.54,95% CI=0.26～1.11).而两位点联合作用分析发现与携带219RR,883MM或883MI基因型者相比较,携带其他组合基因型的个体冠心病患病风险降低61%(OR=0.39,95% CI=0.26～0.60).另外,对照组中携带219K等位基因者血清HDL-C水平显著高于219K非携带者 (P=0.037),提示Arg219Lys位点的多态改变主要通过改变HDL-C水平影响个体冠心病的患病风险.结论 ABCA1 R219K可能与中国汉族人群冠心病遗传易感性有关,血清高密度脂蛋白可能是其作用靶点.
Objective To investigate the association of R219K and M883I polymorphisms of ATP binding cassette transporter 1 gene with lipid metabolism and the susceptibility to coronary atherosclerotic heart disease in Chinese population. Methods Genotypes were determined by PCR-restriction fragment length polymorphism and Primer introduced restriction analysis-PCR techniques, respectively, in 248 unrelated CHD-free controls and 224 CHD cases. Results Smoking, high blood pressure and high serum glucose were independent risk factors for CHD. Multivariate logistic regression analysis revealed that individuals carrying at least one 219K variant allele （ RK ＋ KK genotypes） had a significantly decreased risk for CHD （adjusted OR =0. 41; 95% CI = 0. 27 - 0. 61 ） compared with the wild-type genotype （219RR） and only 88311 homozygotes displayed a decreased risk for CHD （adjusted OR = 0. 54; 95% CI = 0. 26 - 1.11 ） compared with 883MM and 883MI genotypes. Furthermore, compared with individuals with both wild genotypes （219 RR and 883 MM or 883 MI） other individuals with all other assembly genotypes had a significantly decreased risk （adjusted OR = 0. 39, 95% CI = 0. 26 - 0. 60）. Plasma HDL-C in 219K allele carriers were markedly higher than those in 219 K non-carriers in controls （P = 0. 037 ）. Conclusion The ABCA1 R219K polymorphism may be involved in the variability of serum HDL-C and the susceptibility to coronary artery disease.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2005年第7期627-630,共4页
Chinese Journal of Cardiology
基金
江苏省卫生厅科技基金会重大科研课题(H200218)
