Comprehensive evaluation of allele frequency differences of MC1R variants across populations
Comprehensive evaluation of allele frequency differences of MC1R variants across populations
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DOI：
10.1002/humu.20476
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发表时间：
2007-05-01
期刊：
影响因子：
3.9
通讯作者：
Landi, Maria Teresa
中科院分区：
文献类型：
--
作者：
Gerstenblith, Meg R.;Goldstein, Alisa M.;Landi, Maria Teresa
黑素皮质素1受体(MC1R)是G蛋白偶联受体超家族的一员，介导对黑素皮质素的反应，目前是人类正常色素变异的最佳贡献者。在不同的人群中已经发现了大量的MC1R基因的自然多态或变种。其中一些变异与特定的头发和肤色表型、雀斑的存在以及黑色素瘤和非黑色素瘤皮肤癌的风险有关。有趣的是，一些MC1R变异体除了对色素沉着有影响外，还与皮肤癌有关。虽然在凯尔特人中，红色头发变种(RHC变种)与皮肤癌风险有关，但在深色高加索人群中的研究已经证明，非RHC MC1R变种对皮肤癌风险也很重要。我们回顾和比较了不同地理区域的MC1R变异的等位基因频率差异。我们观察到变异在不同种群中的分布有很大的差异，浅色和深色的个体之间有显著的差异。此外，在高加索人群中，有7个变异体(p.V60L、p.V92M、p.D84E、p.R151C、p.R160W、p.R163Q和p.D294H)的等位基因频率存在显著差异。探索不同色素沉着和不同皮肤癌风险的人群中MC1R变异的等位基因频率的差异可能有助于我们更好地理解MC1R、色素沉着和癌症发生之间的复杂关系。
The melanocortin 1 receptor (MC1R), a member of the G protein-coupled receptors superfamily, mediates the response to melanocortins and is currently the best-described contributor to normal pigment variation in humans. A remarkably large number of natural polymorphisms, or variants, of the MC1R gene have been identified in different populations. Some of these variants have been associated with specific hair and skin color phenotypes, the presence of freckling, and melanoma and nonmelanoma skin cancer risk. Interestingly, some MC1R variants have been associated with skin cancer beyond their effects on pigmentation. Although the red hair color variants (RHC variants) have been associated with skin cancer risk in the Celtic population, studies in darkly-pigmented Caucasian populations have demonstrated the importance of non-RHC MC1R variants on skin cancer risk as well. We have reviewed and compared allele frequency differences of MC1R variants across geographic regions. We observed large differences in the distribution of variants across populations, with a prominent difference between lightly and darkly-pigmented individuals. Moreover, among Caucasian groups, there were seven variants (p.V60L, p.V92M, p.D84E, p.R151C, p.R160W, p.R163Q, and p.D294H) with significantly different allele frequencies. Exploring differences in allele frequencies of MC1R variants across populations with varying pigmentation and differing skin cancer risk may improve our understanding of the complex relationship between MC1R, pigmentation, and carcinogenesis.