APOA1/C3/A4/A5基因簇的新载脂蛋白基因:APOA5及其研究进展  

A Novel Gene in APOA1/C3/A4/A5 cluster : Apolipoprotein A5

作　　者：刘合焜[1] 张思仲[1] 苏智广[1] 马用信[1] 王春婷[2] 

机构地区：[1]四川大学华西医院医学遗传学研究室 [2]福建医科大学细胞生物学与遗传学系,福州350004

出　　处：《遗传》2004年第6期953-956,共4页Hereditas（Beijing)

基　　金：国家"8 63"高技术项目No .2 0 0 1AA2 2 40 2 10 3 ;2 0 0 2BA711A0 8~~

摘　　要：应用人和鼠的比较基因组学和功能基因组学方法 ,Pennaccio等和Vliet等分别在APOA1/C3/A4基因簇中发现新的载脂蛋白基因APOA5。人的APOA5基因编码 36 6个氨基酸 ,与人APOA4、小鼠Apoa5高度同源。APOA5转基因小鼠其甘油三酯 (TG)减少至野生型的 1/3,而Apoa5基因敲除小鼠其TG却增加 4倍。APOA5多态位点SNP3( 1131T >C)和S19W及单倍型APOA5 3有显著升高TG的作用。APOA5调节血浆TG水平的作用与APOC3作用相反 。Using methods of comparative and functional genomics, a new gene coding for apolipoprotein A5 was identified in the vicinity of APOA1/C3/A4 cluster on human chromosome 11q23 by Pennaccio team and Vliet team. The open reading frame of human APOA5 encoded a 366-amino acid protein with high sequence homology to mouse Apoa5 and human APOA4. Mice expressing a human APOA5 transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoa5 had four times as much plasma triglycerides as controls. Single nucleotide polymorphisms (SNPs) in APOA5 (S19W, -1131T>C) and APOA5 haplotype (APOA5*3) were independently associated with high plasma triglyceride levels. These findings indicate that APOA5 is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.

关 键 词：载脂蛋白APOA5 APOA5基因 甘油三酯 冠心病 

分 类 号：R543[医药卫生—心血管疾病]