Newman Dina L, Abney Mark, Dytch Harvey, Parry Rodney, McPeek Mary Sara, Ober Carole
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Hum Mol Genet. 2003 Jan 15;12(2):137-44. doi: 10.1093/hmg/ddg012.
Serum triglyceride (TG) level is a well-known risk factor for cardiovascular disease, a leading cause of morbidity and mortality in Western countries. Although genome-wide scans for TG have been conducted in several populations, few loci have shown strong evidence for linkage. The Hutterites are a founder population, which practices a communal lifestyle that includes a uniformly high-fat, high-cholesterol diet. We measured serum TG in 485 Hutterites >or=14 years old and performed a genome-wide scan to find genetic determinants of the observed variation in TG levels, using mapping methods that take advantage of the extensive inbreeding and linkage disequilibrium (LD) in this single, 1623-member pedigree. We report two highly significant associations with TG levels, alleles at D2S410 on 2q14 (locus P=5.8 x 10(-6), genome-wide P=0.005) and at IFNA on chromosome 9p21 (locus P=4.3 x 10(-5), genome-wide P=0.024). In each case, homozygosity at the locus is associated with low TG levels, suggesting that alleles at nearby loci may protect against high TG levels.
血清甘油三酯（TG）水平是心血管疾病的一个众所周知的危险因素，而心血管疾病是西方国家发病和死亡的主要原因。尽管已经在几个人群中进行了全基因组扫描以寻找与TG相关的基因座，但很少有基因座显示出强有力的连锁证据。哈特派是一个始创人群，他们实行集体生活方式，包括统一的高脂肪、高胆固醇饮食。我们测量了485名年龄≥14岁的哈特派人群的血清TG，并进行了全基因组扫描，以利用这个由1623名成员组成的单一谱系中广泛的近亲繁殖和连锁不平衡（LD），通过定位方法找到观察到的TG水平变异的遗传决定因素。我们报告了两个与TG水平高度显著相关的基因座，位于2q14的D2S410等位基因（基因座P = 5.8 x 10^(-6)，全基因组P = 0.005）和位于9p21的IFNA等位基因（基因座P = 4.3 x 10^(-5)，全基因组P = 0.024）。在每种情况下，该基因座的纯合性都与低TG水平相关，这表明附近基因座的等位基因可能对高TG水平具有保护作用。
