ADH1B 和 ALDH2 中的功能变异与日本人群的全因死亡率非相加相关。,European Journal of Human Genetics

当前位置： X-MOL 学术 › Eur. J. Hum. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

ADH1B 和 ALDH2 中的功能变异与日本人群的全因死亡率非相加相关。
European Journal of Human Genetics ( IF 3.7 ) Pub Date : 2019-09-26 , DOI: 10.1038/s41431-019-0518-y
Saori Sakaue _{1,

2,

3} , Masato Akiyama _{1,

4} , Makoto Hirata ₅ , Koichi Matsuda ₆ , Yoshinori Murakami ₇ , Michiaki Kubo ₈ , Yoichiro Kamatani _{1,

9} , Yukinori Okada _{2,

10}

Affiliation

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, 113-8655, Japan.
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Laboratory of Genome Technology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan.
Division of Molecular Pathology, the Institute of Medical Sciences, the University of Tokyo, Tokyo, 108-8639, Japan.
RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Tokyo, 108-8639, Japan.
Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, 565-0871, Japan.

涉及酒精代谢的功能变异，即 ADH1B 中 rs1229984:A > G 的 A 等位基因和 ALDH2 中 rs671:G > A 的 A 等位基因，在东亚人群中特别普遍。他们被证明是在最近的积极选择下，但选择的原因未知。为了测试这些阳性选择的变异是否对现代人群的生存有有益影响，我们使用具有基因型和随访生存数据的大规模日本队列（n = 135,974）进行了生存分析。rs671-A 等位基因与加性模型中更好的存活率显着相关（死亡率的 HR = 0.960，P = 1.7 × 10-5），并且 rs1229984-A 具有加性和非加性效应（HR = 0.962， P = 0.0016 和 HR = 0.958，P = 0.0066，分别），这与正选择一致。这些等位基因对生存的有利影响与饮酒习惯本身无关。还观察到 rs1229984 和 rs671 基因型之间的异质组合效应（rs671 处 AA 基因型的 HR 分别为 1.03、0.80 和 0.90，而 rs1229984 处的 GG、GA 和 AA 基因型分别反映了对生存的协同效应。

"点击查看英文标题和摘要"

Functional variants in ADH1B and ALDH2 are non-additively associated with all-cause mortality in Japanese population.

The functional variants involved in alcohol metabolism, the A allele of rs1229984:A > G in ADH1B and the A allele of rs671:G > A in ALDH2, are specifically prevalent among East Asian population. They are shown to be under recent positive selection, but the reasons for the selection are unknown. To test whether these positively selected variants have beneficial effects on survival in modern population, we performed the survival analyses using the large-scale Japanese cohort (n = 135,974) with genotype and follow-up survival data. The rs671-A allele was significantly associated with the better survival in the additive model (HR for mortality = 0.960, P = 1.7 × 10-5), and the rs1229984-A had both additive and non-additive effects (HR = 0.962, P = 0.0016 and HR = 0.958, P = 0.0066, respectively), which was consistent with the positive selection. The favorable effects of these alleles on survival were independent of the habit of alcohol consumption itself. The heterogenous combinatory effect between rs1229984 and rs671 genotype was also observed (HRs for AA genotype at rs671 were 1.03, 0.80, and 0.90 for GG, GA, and AA genotype at rs1229984, respectively), supposedly reflecting the synergistic effects on survival.

更新日期：2019-09-26

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南