Hodoglugil Ugur, Tanyolaç Sinan, Williamson David W, Huang Yadong, Mahley Robert W
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA, USA.
J Lipid Res. 2006 Jan;47(1):144-53. doi: 10.1194/jlr.M500343-JLR200. Epub 2005 Oct 28.
The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in approximately 3,000 subjects. The rare alleles of the -1464T>C, -1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19-86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the -1464T>C polymorphism had no effect by itself but was a marker for the -1131T>C, S19W, and 1259T>C polymorphisms. The -1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 -1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California.
载脂蛋白A-V基因（APOA5）在决定血浆甘油三酯水平方面起着重要作用。我们研究了APOA5基因多态性对土耳其人群血浆甘油三酯水平的影响，该人群高密度脂蛋白胆固醇水平较低且冠状动脉疾病患病率较高。我们发现了15种多态性，其中3种是新发现的。选择了7个单倍型标签单核苷酸多态性（SNP）并在约3000名受试者中进行基因分型。-1464T>C、-1131T>C、S19W和1259T>C这几个SNP的罕见等位基因与甘油三酯水平升高显著相关（升高19 - 86mg/dl；P<0.05），且具有明显的基因剂量效应。对9种常见APOA5单倍型进行单倍型分析显示，其对甘油三酯水平有显著影响（P<0.001）。对单倍型的详细分析清楚地表明，-1464T>C多态性本身没有影响，但它是-1131T>C、S19W和1259T>C多态性的一个标记。-1131T>C和1259T>C多态性处于强但不完全的连锁不平衡状态，似乎具有独立效应。因此，APOA5基因的-1131T>C、S19W和1259T>C罕见等位基因与血浆甘油三酯水平显著升高相关。在大约40%的土耳其人中至少存在这些等位基因中的一个。在居住在加利福尼亚州旧金山的美国白人中也观察到了-1131T>C和S19W的类似关联。
