Hutter Carolyn M, Austin Melissa A, Farin Federico M, Viernes Hannah-Malia, Edwards Karen L, Leonetti Donna L, McNeely Marguerite J, Fujimoto Wilfred Y
Department of Epidemiology, Institute for Public Health Genetics, School of Public Health and Community Medicine, University of Washington, 1959 N.E. Pacific Avenue, Box 357236, Seattle, WA 98195, USA.
Atherosclerosis. 2006 Mar;185(1):78-86. doi: 10.1016/j.atherosclerosis.2005.05.033. Epub 2005 Jul 14.
The LIPG gene on chromosome 18 encodes for endothelial lipase, a member of the triglyceride lipase family. Mouse models suggest that variation in LIPG influences high-density lipoprotein (HDL) metabolism, but only limited data are available in humans. This study examined associations of LIPG haplotypes, comprising a single nucleotide polymorphism (SNP) in the promoter region (-384A>C), and a nonsynonymous SNP in exon 3 (Thr111Ile or 584C>T), with lipoprotein risk factors in 541 adult Japanese Americans. A marginal association was found between LIPG diplotypes and HDL cholesterol (p=0.045). Stronger associations were seen for HDL3 cholesterol (p=0.005) and Apolipoprotein AI plasma levels (p=0.002). After adjustment for age, gender, smoking and medications, individuals homozygous for the minor allele at both SNPs (*4 haplotype) had a more favorable risk factor profile, compared to other haplotype combinations. No relationship was seen for plasma triglyceride levels or low-density lipoprotein (LDL) size, but the homozygous *4 diplotype was also associated with lower Apolipoprotein B and LDL cholesterol levels (p=0.001 and 0.015, respectively). In conclusion, this community-based family study of Japanese Americans demonstrates that LIPG variants are associated with HDL related risk factors, and may play a role in susceptibility to cardiovascular disease in this population.
位于18号染色体上的LIPG基因编码内皮脂肪酶，它是甘油三酯脂肪酶家族的一员。小鼠模型表明，LIPG基因的变异会影响高密度脂蛋白（HDL）的代谢，但在人类中仅有有限的数据。本研究在541名成年日裔美国人中，检测了由启动子区域的一个单核苷酸多态性（SNP）（-384A>C）和外显子3中的一个非同义SNP（Thr111Ile或584C>T）组成的LIPG单倍型与脂蛋白风险因素之间的关联。发现LIPG双倍型与HDL胆固醇之间存在边缘关联（p=0.045）。在HDL3胆固醇（p=0.005）和载脂蛋白AI血浆水平（p=0.002）方面观察到更强的关联。在对年龄、性别、吸烟和药物进行校正后，与其他单倍型组合相比，两个SNP处均为次要等位基因纯合子的个体（4单倍型）具有更有利的风险因素谱。血浆甘油三酯水平或低密度脂蛋白（LDL）大小未见相关性，但纯合4双倍型也与较低的载脂蛋白B和LDL胆固醇水平相关（分别为p=0.001和0.015）。总之，这项基于社区的日裔美国人家庭研究表明，LIPG变异与HDL相关风险因素有关，可能在该人群的心血管疾病易感性中起作用。
