Pennacchio Len A, Olivier Michael, Hubacek Jaroslav A, Krauss Ronald M, Rubin Edward M, Cohen Jonathan C
Genome Sciences Department, MS 84-171, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720, USA.
Hum Mol Genet. 2002 Nov 15;11(24):3031-8. doi: 10.1093/hmg/11.24.3031.
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 APOA52) that is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA53) 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 APOA53 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 APOA53 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA53 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 APOA52 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.
最近发现的载脂蛋白A5基因（APOA5）已被证明在决定人类和小鼠的血浆甘油三酯浓度方面发挥重要作用。我们之前鉴定出一种APOA5单倍型（命名为APOA52），约16%的高加索人携带该单倍型，它与血浆甘油三酯浓度升高有关。在本报告中，我们描述了另一种APOA5单倍型（APOA53），它包含单核苷酸多态性c.56C>G的罕见等位基因，该突变使第19密码子处的丝氨酸变为色氨酸，并且在三个不同人群中均独立地与高血浆甘油三酯水平相关。在一个由264名血浆甘油三酯浓度高于第90百分位数或低于第10百分位数的高加索男性和女性组成的样本中，APOA53单倍型在高血浆甘油三酯水平组中的出现频率是低血浆甘油三酯水平组的三倍多。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时以及高碳水化合物饮食和高脂肪饮食后接受研究，APOA53单倍型在所有三种饮食方案下均与血浆甘油三酯水平升高相关。在第三个由2660名随机选择的个体组成的人群中，12%的高加索人、14%的非裔美国人以及28%的西班牙裔携带APOA53单倍型，并且在每个种族群体的男性和女性中，该单倍型均与血浆甘油三酯水平升高相关。这些发现表明，APOA5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。总之，25%至50%的非裔美国人、西班牙裔和高加索人携带APOA52和APOA5*3单倍型，这支持了常见人类变异对普通人群数量性状表型的贡献。
