Genetic variants in PCSK9 in the Japanese population:: Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population
Genetic variants in PCSK9 in the Japanese population:: Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population
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DOI：
10.1016/j.atherosclerosis.2006.12.035
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发表时间：
2008-01-01
期刊：
影响因子：
5.3
通讯作者：
Miyata, Toshiyuki
中科院分区：
文献类型：
--
作者：
Miyake, Yasuko;Kimura, Rina;Miyata, Toshiyuki
本研究旨在探讨普通人群血浆低密度脂蛋白胆固醇（LDL - C）水平是否受PCSK9基因罕见序列变异的影响。我们对普通人群中LDL - C水平最低（n = 78）和最高（n = 96）的个体以及服用抗高胆固醇血症药物的个体（n = 96）的PCSK9基因启动子和编码区进行了测序（总人数n = 3655）。我们在PCSK9基因中鉴定出33种序列变异，其中24种为日本人所特有。统计分析表明，一种错义突变R93C与低LDL - C水平相关。其他变异与LDL - C水平无关，或者携带这些变异的个体数量太少，无法进行统计分析。对低LDL - C组和高LDL - C/治疗组之间非同义突变个体数量的比较发现，四种错义突变和一种无义突变仅在低LDL - C组中被发现，六种错义突变仅在高LDL - C/治疗组中被发现。由于我们分析了LDL - C水平处于两端的人群，这些非同义突变中的一些可能与日本人群的低或高LDL - C水平相关。与LDLR或apoB - 100相比，鉴于PCSK9中非同义突变的频率极高，PCSK9突变可能是累积影响普通人群血浆LDL - C水平的重要因素。（C）2007爱思唯尔爱尔兰有限公司。保留所有权利。
The aim of this Study was to investigate whether plasma low-density lipoprotein cholesterol (LDL-C) levels in the general population are influenced by rare sequence variations in the PCSK9 gene. We sequenced the promoter and coding regions of the PCSK9 gene in individuals from the general population (n = 3655) with the lowest (n = 78) and highest (n = 96) LDL-C levels and in individuals taking antihypercholesterolemia medication (n = 96). We identified 33 sequence variants in the PCSK9 gene among which 24 were specific for Japanese. Statistical analysis showed that one missense mutation, R93C, was associated with low LDL-C levels. The other variants had no association with LDL-C levels or the numbers of individuals with the variants were too small for statistical analysis. A comparison of the numbers of individuals with nonsynonymous mutations between the low LDL-C and high LDL-C/treatment groups found that four missense mutations and one nonsense mutation were identified only in the low LDL-C group and six missense mutations were identified only in the high LDL-C/treatment group. As we have analyzed groups at opposite ends of the LDL-C spectrum, it is likely that some of these nonsynonymous mutations may be associated with either low or high LDL-C in the Japanese population. Based on the extremely high frequencies of the nonsynonymous mutations in PCSK9 compared with those of LDLR or apoB-100, PCSK9 mutations could be important factors that cumulatively influence plasma LDL-C levels in the general population. (C) 2007 Elsevier Ireland Ltd. All rights reserved.