Association study confirms the role of two OCA2 polymorphisms in normal skin pigmentation variation in East Asian populations
Association study confirms the role of two OCA2 polymorphisms in normal skin pigmentation variation in East Asian populations
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DOI：
10.1002/ajhb.22678
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发表时间：
2015-07-01
影响因子：
2.9
通讯作者：
Parra, Esteban J.
中科院分区：
文献类型：
--
作者：
Eaton, Katherine;Edwards, Melissa;Parra, Esteban J.
目的 本研究的主要目的是测试位于 9 个色素沉着候选基因内的 18 个多态性与生活在加拿大的东亚血统个体样本 (N=419) 中收集的定量皮肤色素沉着测量值之间的关联。方法这 18 个多态性位于显示东亚人群正选择的推定特征的基因内。根据东亚常见多态性的注释选择遗传标记进行基因分型，以预测潜在的功能效应。我们将注意力限制在东亚人群与非洲和欧洲人群之间等位基因频率差异至少 30% 的多态性，或者具有东亚人中存在但非洲人和欧洲人中不存在的等位基因。结果在 OCA2 基因中选择的两个非同义变异 rs1800414 (His615Arg) 和 rs74653330 (Ala481Thr) 显着与样本中的黑色素水平相关。这两种单核苷酸多态性 (SNP) 都是非同义多态性，位于 15 号染色体上，相距超过 30 kb，并且在东亚样本中的频率非常不同。此外，预计这两种多态性都会对蛋白质产生有害影响。使用加法模型的线性回归分析表明，衍生的 rs1800414 等位基因 G 的每个副本使黑色素指数降低约 0.9 个单位，衍生的 rs74653330 等位基因 A 的每个副本使黑色素指数降低约 1.9 个单位。 结论 两个非同义 OCA2 多态性（rs1800414 和 rs74653330）与东部地区正常皮肤色素沉着变化独立相关亚洲人口在东亚的频率分布有很大不同。是。 J.哼。生物。 27:520-525，2015 年。(c) 2015 年 Wiley 期刊公司。
ObjectivesThe main goal of the study was to test the association of 18 polymorphisms located within nine pigmentation candidate genes with quantitative skin pigmentation measures collected in a sample of individuals of East Asian ancestry living in Canada (N=419).MethodsThe 18 polymorphisms are located within genes that show putative signatures of positive selection in East Asian populations. The genetic markers were selected for genotyping based on an annotation of common East Asian polymorphisms to predict potential functional effects. We restricted our attention to polymorphisms that have an allele frequency difference of at least 30% between East Asian populations and African and European populations, or have alleles that are present in East Asians, but are absent in Africans and Europeans.ResultsTwo nonsynonymous variants selected within the OCA2 gene, rs1800414 (His615Arg) and rs74653330 (Ala481Thr), were significantly associated with melanin levels in the sample. Both single nucleotide polymorphisms (SNPs) are nonsynonymous polymorphisms located more than 30 kb apart on chromosome 15 and have very different frequencies in the East Asian sample. Additionally, both polymorphisms are predicted to have a deleterious effect on the protein. Linear regression analysis using an additive model indicate that each copy of the derived rs1800414 allele G decreases Melanin Index approximately 0.9 units and each copy of the derived rs74653330 allele A decreases Melanin Index approximately 1.9 units.ConclusionsTwo nonsynonymous OCA2 polymorphisms (rs1800414 and rs74653330) are independently associated with normal skin pigmentation variation in East Asian populations and have very different frequency distributions in East Asia. Am. J. Hum. Biol. 27:520-525, 2015. (c) 2015 Wiley Periodicals, Inc.