PCSK9基因5′UTR区rs45448095基因多态性与血浆LDL-C水平的相关性

Correlation of PCSK9 5′ UTR rs45448095 Polymorphism with Plasma LDL-C Levels

目的:探讨前蛋白转化酶枯草溶菌素9(PCSK 9)基因5端非编码区(5′UTR)rs45448095基因多态性与血浆低密度脂蛋白(LDL)水平及冠心病风险的相关性。方法:使用千人基因组计划数据库分析中国汉族人群PCSK 9基因5′UTR区基因多态性,利用荧光报告实验验证候选SNP位点的功能;收集96例健康对照人群(对照组)和96例冠心病患者(疾病组)的外周血,利用Sanger法完成rs45448095位点测序,应用Logistic回归分析对照组人群中rs45448095不同基因型与血脂水平的关系,分析对照组和疾病组人群rs45448095不同基因型与冠心病风险的相关性。结果:中国汉族人群中PCSK 9基因5′UTR区存在rs45448095(MAF>0.05),荧光报告基因实验显示在多个细胞系中(293T/L02)rs45448095-T比rs45448095-C表达显著下降(P<0.0001);对照组人群中携带rs45448095-T基因多态性有更低水平的LDL水平[β(SE)=-0.353(0.158),t=-2.237,P=0.028],rs45448095不影响冠心病的发病风险。结论:PCSK 9基因5′UTR区上一个有功能的rs45448095突变可影响血浆LDL水平。

Objective:To investigate the correlation of a PCSK95′-untranslated region(5′UTR)rs45448095 polymorphism with plasma LDL-C levels and coronary heart disease(CHD).Methods:A process of bioinformatic analysis was used to analyze the PCSK95'UTR polymorphism in Chinese Han Group.Luciferase report assays were used to verify the function of variant.96 controls and 96 people with Chinese Han CHD were collected.The logistic regression was used to analyze the correlation of a PCSK95′UTR rs45448095 polymorphism with plasma LDL-C levels and CHD.Results:There was a common SNP rs45448095 in PCSK95'UTR.Both in L02 and 293T cells,the luciferase reporter activity of the PGL3-T vector(containing T allele of rs45448095)decreased significantly(P<0.0001)when compared with the PGL3-C construct(containing c allele of 45448095).Furthermore,the T allele was significantly related with the decreased LDL-C levels[β(SE)=-0.353(0.158),t=-2.237,P=0.028].Finally,the case-control study suggested that the rs45448095 polymorphism is related with CHD risk.Conclusions:The potential functional variant in 5'UTR of PCSK9,rs45448095 can effect Chinese Han plasma LDL-C levels.