Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels
Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels
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DOI：
10.1093/hmg/11.24.3031
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发表时间：
2002-11-15
影响因子：
3.5
通讯作者：
Cohen, JC
中科院分区：
文献类型：
--
作者：
Pennacchio, LA;Olivier, M;Cohen, JC
最近发现的载脂蛋白A5基因（APOA 5）已被证明在确定人类和小鼠的血浆甘油三酯浓度中发挥重要作用。我们先前鉴定了一种APOA 5单倍型（命名为APOA 5 *2），该单倍型在16%的高加索人中存在，并与血浆甘油三酯浓度升高相关。在这份报告中，我们描述了另一个载脂蛋白A5单倍型（APOA 5 *3），包含罕见的等位基因的单核苷酸多态性c.56C>G，改变丝氨酸色氨酸在密码子19和独立相关的高血浆甘油三酯水平在三个不同的人群。在264例血浆甘油三酯浓度高于第90百分位数或低于第10百分位数的白人男性和女性样本中，APOA 5 *3单倍型在高血浆甘油三酯水平组中的常见程度超过3倍。在第二个独立确定的高加索男性和女性样本（n=419）中，他们在食用自选饮食以及高碳水化合物饮食和高脂肪饮食后进行了研究，APOA 5 *3单倍型与所有三种饮食方案的血浆甘油三酯水平升高相关。在由2660名随机选择的个体组成的第三个人群中，在12%的白人、14%的非洲裔美国人和28%的西班牙裔美国人中发现了APOA 5 *3单倍型，并且与每个种族中男性和女性的血浆甘油三酯水平升高相关。这些发现证实APOA 5基因座对人类血浆甘油三酯水平的个体间差异有显著贡献。总的来说，APOA 5 *2和APOA 5 *3单倍型在25-50%的非洲裔美国人、西班牙裔和高加索人中发现，并支持普通人群中常见人类变异对定量表型的贡献。
The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in similar to16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n=419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12% of Caucasians, 14% of African-Americans and 28% of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.