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全基因组关联研究表明,色素基因在皮肤衰老中起作用。

Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging.

机构信息

QIMR Berghofer Medical Research Institute, Brisbane, Australia.

QIMR Berghofer Medical Research Institute, Brisbane, Australia.

出版信息

J Invest Dermatol. 2017 Sep;137(9):1887-1894. doi: 10.1016/j.jid.2017.04.026. Epub 2017 May 11.

Abstract

Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait at genome-wide significance (P = 4.1 × 10); to our knowledge this is previously unreported. We also confirm previously identified loci, rs12203592 near IRF4 (P = 8.8 × 10) and rs4268748 near MC1R (P = 1.2 × 10). At all three loci we highlight putative functionally relevant SNPs. There are a number of red hair/low pigmentation alleles of MC1R; we found that together these MC1R alleles explained 4.1% of variance in skin pattern damage. We also show that skin aging and reported experience of sunburns was proportional to the degree of penetrance for red hair of alleles of MC1R. Our work has uncovered genetic contributions to skin aging and confirmed previous findings, showing that pigmentation is a critical determinant of skin aging.

摘要

皮肤细微结构模式丧失是衰老和光老化的标志。研究遗传对皮肤模式的影响为深入了解这一影响皮肤外观和角质形成细胞皮肤癌风险的特征提供了机会。我们对来自三个独立队列的 1671 对双胞胎和 1745 名单卵双胞胎(共 5087 人)的皮肤模式(微观形貌评分)损伤的全基因组关联研究进行了荟萃分析。我们发现 SLC45A2 附近的 rs185146 与皮肤衰老特征相关,达到全基因组显著水平(P=4.1×10);据我们所知,这是以前未报道过的。我们还证实了先前鉴定的位于 IRF4 附近的 rs12203592(P=8.8×10)和位于 MC1R 附近的 rs4268748 位点与皮肤老化相关(P=1.2×10)。在这三个位点上,我们都强调了可能具有功能相关性的 SNP。MC1R 存在许多红发/低色素等位基因;我们发现,这些 MC1R 等位基因共同解释了皮肤模式损伤 4.1%的变异。我们还表明,皮肤衰老和报告的晒伤经历与 MC1R 等位基因的红发穿透程度成正比。我们的工作揭示了皮肤老化的遗传贡献,并证实了先前的发现,表明色素沉着是皮肤老化的关键决定因素。

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