Smith R, Healy E, Siddiqui S, Flanagan N, Steijlen P M, Rosdahl I, Jacques J P, Rogers S, Turner R, Jackson I J, Birch-Machin M A, Rees J L
Department of Dermatology, University of Newcastle upon Tyne, UK.
J Invest Dermatol. 1998 Jul;111(1):119-22. doi: 10.1046/j.1523-1747.1998.00252.x.
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.
人类促黑素皮质素1受体（MC1R）基因变异与红头发及白皙皮肤之间关联的确定，以及该基因变异与动物毛色之间的关系，表明MC1R是正常色素沉着表型中的一个重要控制点。为了进一步明确MC1R变异对正常人群色素沉着的影响，我们在爱尔兰普通人群的一系列个体中寻找该基因的改变，该人群中皮肤白皙类型的个体占多数。75%的个体MC1R基因存在变异，30%的个体含有两种变异。Arg151Cys、Arg160Trp和Asp294His变异与红头发显著相关（分别为p = 0.0015、p < 0.001和p < 0.005）。重要的是，携带这三种变异中两种的个体均为红头发，尽管有些红头发个体仅表现出一种改变。使用改良的菲茨帕特里克量表评估发现，这三种相同的变异在皮肤白皙类型的个体中也占比过高。尽管存在这些关联，但许多深色头发/深色皮肤类型的受试者也携带MC1R变异，不过没有证据表明变异与较深表型存在任何特定关联。Asp294His变异在荷兰人群中同样与红头发相关，但在瑞典的红发受试者中很少见。在英国人群中，Asp294His变异也与非黑素瘤皮肤癌显著相关。结果表明，Arg151Cys、Arg160Trp和Asp294His变异在决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，红头发特征以及在某些情况下白皙皮肤类型是作为孟德尔隐性性状遗传的。
