Duffy David L, Box Neil F, Chen Wei, Palmer James S, Montgomery Grant W, James Michael R, Hayward Nicholas K, Martin Nicholas G, Sturm Richard A
Queensland Insititute of Medical Research, Brisbane, Australia.
Hum Mol Genet. 2004 Feb 15;13(4):447-61. doi: 10.1093/hmg/ddh043. Epub 2004 Jan 6.
The relationships between MC1R gene variants and red hair, skin reflectance, degree of freckling and nevus count were investigated in 2331 adolescent twins, their sibs and parents in 645 twin families. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed, four common alleles were strongly associated with red hair and fair skin (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were separately combined for the purposes of this analysis and designated as strong 'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color. MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs. This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a R/R genotype (but not R/r), those who also had brown eyes had a mole count twice that of those with blue eyes. This suggests that other OCA2 polymorphisms influence mole count and remain to be described.
在645个双胞胎家庭的2331名青少年双胞胎、他们的兄弟姐妹及父母中，研究了黑素皮质素1受体（MC1R）基因变异与红头发、皮肤反射率、雀斑程度及痣数之间的关系。每个MC1R变异等位基因的外显率与一种等位基因模型一致，即对红头发的影响是相乘的，而对皮肤反射率的影响是相加的。在检测的9个MC1R变异等位基因中，4个常见等位基因与红头发和白皙皮肤密切相关（Asp84Glu、Arg151Cys、Arg160Trp和Asp294His），另外3个等位基因的外显率较低（Val60Leu、Val92Met和Arg163Gln）。为了进行该分析，将这些变异分别组合，并指定为强“R”（比值比=63.3；95%可信区间31.9 - 139.6）和弱“r”（比值比=5.1；95%可信区间2.5 - 11.3）红头发等位基因。红头发个体主要出现在R/R和R/r组，分别占67.1%和10.8%。为了评估褐眼颜色基因OCA2对变异MC1R等位基因表型效应的相互作用，我们将眼睛颜色作为协变量，并对两个OCA2单核苷酸多态性（Arg305Trp和Arg419Gln）进行基因分型，这两个多态性被证实可改变眼睛颜色。MC1R基因型对皮肤固有颜色、雀斑和痣数的影响因眼睛颜色而改变，但不受这两个OCA2单核苷酸多态性基因型的影响。这可能是由于这些OCA2单核苷酸多态性与褐/绿而非蓝眼颜色相关。在R/R基因型个体（而非R/r个体）中，褐眼个体的痣数是蓝眼个体的两倍。这表明其他OCA2多态性影响痣数，有待进一步描述。
