Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA.
Am J Clin Nutr. 2010 Jun;91(6):1574-83. doi: 10.3945/ajcn.2009.28927. Epub 2010 Apr 21.
Alterations in plasma fatty acid distribution are linked to metabolic abnormalities related to type 2 diabetes and cardiovascular disease.
The aim of this study was to investigate genetic factors influencing plasma fatty acid distribution in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study.
Fatty acids in plasma were measured by gas chromatography in 761 related individuals (>35 y of age).
Quantitative genetic analyses showed that fatty acid distribution is significantly heritable (P < 0.001), with heritabilities ranging from 0.33 to 0.55. A genome-wide scan for plasma fatty acids identified a 20-cM region on chromosome 8 (p12-p21) with a quantitative trait locus for monounsaturated fatty acids (logarithm of odds score = 3.8). The same region had a quantitative trait locus for polyunsaturated fatty acids (logarithm of odds score = 2.6). We genotyped single nucleotide polymorphisms (SNPs) in candidate genes in 8p12-p21 and found a significant association between fatty acids and SNPs in apolipoprotein J (APOJ), lipoprotein lipase (LPL), macrophage scavenger receptor 1 (MSR1), and tumor necrosis factor receptor superfamily member 10b (TNFRSF10B). A Bayesian quantitative trait nucleotide analysis based on a measured genotype model showed that SNPs in LPL, TNFRSF10B, and APOJ had strong statistical evidence of a functional effect (posterior probability > or =75%) on plasma fatty acid distribution.
The results indicate that there is strong genetic influence on plasma fatty acid distribution and that genetic variation in APOJ, LPL, and TNFRSF10B may play a role. The GOCADAN study was registered at www.clinicaltrials.gov as NCT00006192.
血浆脂肪酸分布的改变与 2 型糖尿病和心血管疾病相关的代谢异常有关。
本研究旨在探讨影响阿拉斯加因纽特人冠状动脉疾病遗传（GOCADAN）研究中血浆脂肪酸分布的遗传因素。
通过气相色谱法测量 761 名相关个体（>35 岁）的血浆脂肪酸。
定量遗传分析表明，脂肪酸分布具有显著的遗传性（P<0.001），遗传率范围为 0.33 至 0.55。对血浆脂肪酸的全基因组扫描确定了 8 号染色体（p12-p21）上的一个 20-cM 区域，该区域存在单不饱和脂肪酸的数量性状位点（对数优势评分=3.8）。同一区域存在多不饱和脂肪酸的数量性状位点（对数优势评分=2.6）。我们在 8p12-p21 中候选基因的单核苷酸多态性（SNP）进行基因分型，发现载脂蛋白 J（APOJ）、脂蛋白脂肪酶（LPL）、巨噬细胞清道夫受体 1（MSR1）和肿瘤坏死因子受体超家族成员 10b（TNFRSF10B）中的脂肪酸和 SNP 之间存在显著关联。基于测量基因型模型的贝叶斯数量性状核苷酸分析表明，LPL、TNFRSF10B 和 APOJ 中的 SNP 对血浆脂肪酸分布具有很强的统计学证据（后验概率>或=75%）。
结果表明，血浆脂肪酸分布受遗传因素的强烈影响，APOJ、LPL 和 TNFRSF10B 的遗传变异可能起作用。GOCADAN 研究在 www.clinicaltrials.gov 上注册为 NCT00006192。
