Melanocortin 1 receptor variants in an Irish population
Melanocortin 1 receptor variants in an Irish population
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DOI：
10.1046/j.1523-1747.1998.00252.x
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发表时间：
1998-07-01
影响因子：
6.5
通讯作者：
Rees, JL
中科院分区：
文献类型：
--
作者：
Smith, R;Healy, E;Rees, JL
人类黑皮质素1受体（MC 1 R）基因的变异体与红色毛发和白皙皮肤之间的关联的鉴定，以及该基因的变异体与动物的毛色之间的关系，表明MC 1 R是正常色素沉着表型中的整体控制点。为了进一步确定MC 1 R变异体对正常群体中色素沉着的贡献，我们已经在一系列来自普通爱尔兰人群的个体中寻找了该基因的改变，在这些人群中，具有白色皮肤类型的个体占优势。75%的人在MC 1 R基因中含有一个变体，30%的人含有两个变体。Arg 151 Cys、Arg 160 Trp和Asp 294 His变异与红发显著相关（分别为p = 0.0015、p < 0.001和p < 0.005）。重要的是，没有一个携带这三种变异中的两种的个体没有红头发，尽管一些红头发的个体只显示出一种变异。使用改良的菲茨帕特里克量表评估，相同的三种变体在浅色皮肤类型的个体中也过度表达。尽管有这些关联，许多深色头发/深色皮肤类型的受试者携带MC 1 R变体，但没有证据表明变体与深色表型有任何特定关联，Asp 294 His变体与荷兰人群中的红发相似，但在瑞典的红发受试者中不常见。Asp 294 His变异体也与英国的非黑色素瘤皮肤癌显著相关。人口结果表明，Arg 151 Cys，Arg 160 Trp和Asp 294 His变异体在确定色素沉着表型和对紫外线辐射的反应方面具有关键意义，并表明在许多情况下，红发成分和在某些情况下，白皙皮肤类型是作为孟德尔隐性遗传的。
The identification of an association between variants in the human melanocortin 1 receptor (MC1R) gene and red hair and fair skin, as well as the relation between variants of this gene and coat color in animals, suggests that the MC1R is an integral control point in the normal pigmentation phenotype, In order to further define the contribution of MC1R variants to pigmentation in a normal population, we have looked for alterations in this gene in series of individuals from a general Irish population, in whom there is a preponderance of individuals with fair skin type. Seventy-five per cent contained a variant in the MC1R gene, with 30% containing two variants. The Arg151Cys, Arg160Trp, and Asp294His variants were significantly associated with red hair (p = 0.0015, p < 0.001, and p < 0.005, respectively). Importantly, no individuals harboring two of these three variants did not have red hair, although some red-haired individuals only showed one alteration. The same three variants were also over-represented in individuals with light skin type as assessed using a modified Fitzpatrick scale. Despite these associations many subjects with dark hair/darker skin type harbored MC1R variants, but there was no evidence of any particular association of variants with the darker phenotype, The Asp294His variant was similarly associated with red hair in a Dutch population, but was infrequent in red-headed subjects from Sweden. The Asp294His variant was also significantly associated with nonmelanoma skin cancer in a U.K. population. The results show that the Arg151Cys, Arg160Trp, and Asp294His variants are of key significance in determining the pigmentary phenotype and response to ultraviolet radiation, and suggest that in many cases the red-haired component and in some cases fair skin type are inherited as a Mendelian recessive.