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目的探讨三磷酸腺苷结合盒转运子A1(ATPbindingcassettetransporter1,ABCA1)基因R219K及M883I单核苷酸多态性(SNP)位点与脂代谢和冠心病(coronaryheartdisease,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883G→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ABCA1R219K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 relationship between single nucleotide polymorphisms (SNP) of R219K and M883I and lipid metabolism and susceptibility to coronary heart disease (CHD) in ATPbinding cassette transporter1 (ABCA1) gene. Methods Hospital-based case-control study. Coronary artery disease confirmed by coronary angiography 224 cases, the same area 248 cases of normal control. PCR-RFLP and PIRA-PCR were used to detect codon 219 codon G → A (Arg219Lys) and 883G → A (Met883Ile) ABCA1 codon polymorphisms in different genotypes and individuals to compare the risk of coronary heart disease Relationship. Results Smoking, hypertension and hyperglycemia were independent risk factors for coronary heart disease. Patients with at least one 219K allele (ie, the RK and KK genotypes) had a significantly reduced risk of coronary heart disease by 59% (OR = 0.41, 95% CI = 0.27-0 · 61). However, in the 883 locus, carriers of genotype II had a lower incidence of coronary heart disease (OR = 0.54, 95% CI = 0.26 to 1.11). A combined analysis of the two loci showed a 61% reduction in the risk of coronary heart disease among individuals with other combined genotypes compared with those carrying the 219RR, 883MM or 883MI genotype (OR = 0.39, 95% CI = 0.26 ~ 0.60). In addition, the serum HDL-C level of the 219K allele in control group was significantly higher than that of 219K non-carrier (P = 0 · 037), suggesting that the polymorphism of Arg219Lys locus mainly affects the individual coronary heart disease by changing HDL-C level The risk of illness. Conclusion ABCA1R219K may be related to genetic susceptibility to coronary heart disease in Chinese Han population. Serum high density lipoprotein may be the target of this therapy.