Rare variants in the lipoprotein lipase (LPL) gene are common in hypertriglyceridemia but rare in Type III hyperlipidemia
Rare variants in the lipoprotein lipase (LPL) gene are common in hypertriglyceridemia but rare in Type III hyperlipidemia
复制标题
DOI：
10.1016/j.atherosclerosis.2010.11.026
复制
发表时间：
2011-02-01
期刊：
影响因子：
5.3
通讯作者：
Beil, F. U.
中科院分区：
文献类型：
--
作者：
Evans, D.;Arzer, J.;Beil, F. U.
目的：全基因组关联研究（GWAS）表明，脂蛋白脂酶基因（LPL）的变异与血浆甘油三酯水平相关，但常见变异仅占变异的1.25%。本研究的目的是确定LPL基因罕见变异在各种形式的高脂血症患者中的频率。313例甘油三酯高于年龄和性别第95百分位数的患者LPL基因外显子+外显子/内含子边界的DNA序列（其中107人的甘油三酯高于875毫克/分升）和121例III型高脂血症determined.Results：20种罕见的变异检测，其中7个以前曾报道。所有的罕见变异体都以杂合子的形式存在。16个是错义突变，2个是短缺失突变，有一个无义和插入突变。其中15个错义突变导致了氨基酸的变化。有13名患者（12.1%）甘油三酯高于875 mg/dl，10名患者（4.9%）甘油三酯中度升高，他们是LPL基因中至少一种罕见的非同义突变的携带者。III型HLP的患者，两个罕见的variants.Conclusion载体：罕见的LPL基因突变是常见的甘油三酯升高的患者。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Objective: Genomewide association studies (GWAS) have shown that variation in the lipoprotein lipase gene (LPL) is associated with plasma triglyceride levels but that common variants account for only 1.25% of the variance. The aim of this study was to determine the frequency of rare variants in the LPL gene in patients with various forms of hypertriglyceridemia.Methods: The DNA sequence of the exons plus exon/intron boundaries of the LPL gene of 313 patients with triglycerides above the 95th percentile for age and sex (107 of whom had triglycerides above 875 mg/dl) and 121 patients with Type III hyperlipidemia was determined.Results: Twenty rare variants were detected of which seven have been previously reported. All of the rare variants were present as heterozygotes. Sixteen were missense mutations, two were short deletion mutants and there were single nonsense and insertion mutations. Fifteen of the missense mutations resulted in an amino acid change. There were 13 patients (12.1%) with triglycerides above 875 mg/dl and 10 patients (4.9%) with moderately elevated triglycerides, who were carriers of at least one rare, non-synonymous mutation in the LPL gene. Of the patients with Type III HLP, two were carriers of rare variants.Conclusion: Rare mutations in the LPL gene are frequent in patients with elevated triglycerides. (C) 2010 Elsevier Ireland Ltd. All rights reserved.