LIPC基因突变和冠状动脉粥样硬化性心脏病易感性的关联研究  

Study on the Association of Hepatic Lipase Gene Mutation with the Susceptibility to Coronary Atherosclerotic Heart Disease

作　　者：傅蕾[1] 施海明[1] 黄薇 王颖 罗心平[1] 何仲海[3] 许建中[3] 金慧根 

机构地区：[1]复旦大学附属华山医院心内科 [2]国家人类基因组南方研究中心遗传部,上海200120 [3]上海市长宁区中心医院心内科,上海200050 [4]上海市普陀区中心医院心内科,上海200010

出　　处：《复旦学报（医学版）》2005年第4期443-446,450,共5页Fudan University Journal of Medical Sciences

摘　　要：目的确定肝脂酶(hepaticlipase,HL)LIPC基因9种突变在中国人群中的频率,并探讨这些突变与脂代谢和冠状动脉粥样硬化性心脏病(冠心病,CAD)易感性的关系。方法对224例CAD患者和129例正常人LIPC基因相应位点进行通用TaqMan探针技术的实时荧光PCR方法,检测LIPC基因单核苷酸多态性(SNP)。用HWE软件、STA或SPSS软件分别进行遗传平衡检验和多变量等统计学分析。结果在正常对照组和CAD患者组中LIPC的9个高频SNPs位点均检出突变基因。RS2242064位点突变基因型为A/A、A/C、C/C,其频率在CAD患者组和对照组中分布有显著差异(P=0.019);RS2242064位点突变的等位基因频率分布符合Hardy-Weinberg平衡;在平衡了其他混杂因素的情况下A/C基因型是冠心病的一项独立的危险因素,且非常显著(OR=1.95,P=0.021)。在CAD组中AC突变杂合子与A/A+C/C的患者相比,apo(A)显著降低(P=0.045),HDL显著降低(P=0.02)。结论在中国人群中LIPC的9个高频SNPs位点突变均在入选对象中检出,LIPC基因RS2242064位点突变为A/C基因型可能是中国人的易感因子之一。Purpose To determine the frequencies of 9 SNPs of hepatic lipase (HL) LIPC gene in Chinese po- pulation and to investigate the association of the mutations with lipid metabolism and the susceptibility to coronary atherosclerotic heart disease(CAD). Methods A novel end-point fluorescent PCR method based on universal TaqMan probe was developed to detect 9 SNPs of the target gene LIPC in 224 CAD patients and 129 unrelated control individuals.The test for Hardy-Weinberg equilibrium was performed using HWE,SPSS program and statistical analysis was implemented in statistical package SPSS or STA. Results Nine high frequency SNPs of LIPC gene were found in control and CAD patients.The mutant LIPC genotypes A/A,A/C,C/C were detected in CAD group and control group.Case-control analyses of genotype distributions between the two groups showed significant difference only for the LIPC(RS 2242064).By multivariate analysis of the three mutant genotypes, it showed that the LIPC(RS2242064) polymorphism was independently associated with arterial disease (P<0.01,OR=1.95).Compared with the CAD group without A/C mutation,the A/C heterozygous CAD patients exhibited a significant decrease in plasma HDL-C and apo(A) concentration(P=0.02; P=0.045). Conclusions Variation in LIPC gene (hepatic lipase) associates with clinical outcomes in Chinese patients with established CAD.

关 键 词：冠状动脉粥样硬化性心脏病 LIP Hardy-Weinberg平衡 易感性 C基因突变 关联研究 通用TaqMan探针技术 单核苷酸多态性(SNP) 位点突变 AD患者 SPSS软件 基因频率分布 apo(A) 中国人群 C基因型 PCR方法 统计学分析 正常对照组 

分 类 号：R541.4[医药卫生—心血管疾病] R446.112[医药卫生—内科学]