脂蛋白脂酶基因HindⅢ-S447x单倍型与冠心病的相关研究  

The association of HindⅢ-S447x haplotype in the lipoprotein lipase gene with coronary heart disease

作　　者：冯霞[1] 周新[1] 刘芳[1] 李霞[1] 郑芳[1] 叶光明[1] 陈谦[1] 彭建虹[1] 于连[1] 

机构地区：[1]武汉大学中南医院,430071

出　　处：《中华心血管病杂志》2003年第2期96-100,共5页Chinese Journal of Cardiology

基　　金：湖北省科技攻关项目 ( 2 0 0 0 4 2 7)

摘　　要：目的　探讨脂蛋白脂酶 (LPL)基因第 8内含子HindⅢ限制性内切酶位点及第 9外显子S447x位点突变之间相互关联对血脂和载脂蛋白 (apo)的影响及与冠心病 (CHD)的相关性。方法　采用聚合酶链反应 (PCR)结合限制性片段长度多态性 (RFLP)分析方法 ,分析 1 4 4例无血缘关系的汉族CHD患者 (CHD组 )及 1 2 8例健康体检者 (对照组 )LPL基因S447x位点及HindⅢ位点多态性 ,并进行连锁分析。另外 ,测定血清总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)、apoAI及apoB浓度。结果　LPL两位点多态性之间存在强的连锁不平衡 ,S447x位点X等位基因仅出现在HindⅢ位点H-等位基因的携带者中 ,两位点之间仅存在三种单倍型 :H+S、H-S、H-X ,但三种单倍型在CHD组及对照组的频率无显著差异。排除年龄、体重指数 (BMI)的影响后 ,同H+S单倍型比较 ,CHD组与对照组中H-X单倍型血清TG、LDL C显著降低 (P <0 0 5) ,HDL C水平显著升高 (P <0 0 5) ;同H-S单倍型比较 ,H-X对脂质水平的影响无统计学意义 (P >0 0 5)。结论H-X单倍型可能与血清TG、LDL C水平显著降低、HDL C水平显著升高有关 ,进而可能有降低CHD危险性的作用。但该单倍型和CHD危险性的关系可能主要由于HindⅢ多态性引起 ;Objective To explore the linkage disequilibrium between Ser447stop mutation and HindⅢ polymorphism in the lipoprotein lipase(LPL) gene, its influence on serum lipid and apolipoprotein concentrations, and the association with coronary heart disease (CHD) Methods Polymerase chain reaction amplification and restriction fragment length polymorphism (PCR RFLP) were used to determine Ser447stop mutation and HindⅢ polymorphism in LPL gene in 144 CHD patients and 128 controls Automated Biochemical Analyzer was used to messure the serum total cholesterol (TC)?triglyceride (TG)?high density lipoprotein cholesterol(HDL C)?low density lipoprotein cholesterol(LDL C)?apolipoprotein AI(apoAI) and apolipoprotein B(apoB) Results Significant linkage disequilibrium was observed between the two polymorphisms The X allele at Stop447 site only present with H - allele (no cutting sites)at Hind Ⅲ site and only three haplotypes were found: H +S, H -S and H -X But there was no significant difference in frequencies in the haplotypes between the CHD group and control group Compared with H +S haplotype, the H -X haplotype was associated with significantly lower concentrations of serum TG( P <0 01), TC ( P <0 05),LDL C( P <0 01) and higher concentration of serum HDL C ( P < 0 05). On the contrary, compared with H -S haplotype, the H -X haplotype had no significant effect on the serum lipid and lipoprotein concentrations Conclusion The H -X haplotype is associated with significantly lower concentrations of serum TG?TC?LDL C and higher concentration of HDL C, suggesting a protective effect on CHD There is a very strong linkage disequilibrium between Ser447stop mutation and Hind Ⅲ polymorphism in the LPL gene, but it may not be significant in genetics of CHD throughout Chinese The positive correlation between HindⅢ polymorphism and CHD risk maybe due to its nonrandom association with other functional mutations in the LPL gene besides the Ser447stop mutation

关 键 词：脂蛋白脂酶基因 HindⅢ-S447x单倍型 冠心病 相关研究 

分 类 号：R541.4[医药卫生—心血管疾病]