Bonilla Carolina, Boxill Lesley-Anne, Donald Stacey Ann Mc, Williams Tyisha, Sylvester Nadeje, Parra Esteban J, Dios Sonia, Norton Heather L, Shriver Mark D, Kittles Rick A
Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, 494 Tzagournis Medical Research Facility, 420 W. 12th Avenue, Columbus, OH 43210, USA.
Hum Genet. 2005 Apr;116(5):402-6. doi: 10.1007/s00439-004-1251-2. Epub 2005 Feb 22.
Skin color, a predictor of social interactions and risk factor for several types of cancer, is due to two contrasting forms of melanin, the darker eumelanin and lighter phaeomelanin. The lighter pigment phaeomelanin is the product of the antagonistic function of the agouti signaling protein (ASIP) on the alpha-melanocyte stimulating hormone receptor (MC1R). Studies have shown that a single-nucleotide polymorphism (SNP) in the 3'UTR of the ASIP gene is associated with dark hair and eyes; however, little is known about its role in inter-individual variation in skin color. Here we examine the relationship between the ASIP g.8818A>G SNP and skin color (M index) as assessed by reflectometry in 234 African Americans. Analyses of variance (ANOVA) were performed to evaluate the effects of ASIP genotypes, age, individual ancestry, and sex on skin color variation. Significant effects on M index variation were observed for ASIP genotypes (F(2,236)=4.37, P=0.01), ancestry (F(1,243)=37.2, P<0.001), and sex (F(1,244)=4.08, P=0.05). Subsequent analyses revealed a strong effect on M index from ASIP genotypes in African American females (P<0.001). Our study suggests that the ASIP G>A polymorphism exhibits a dominant effect leading to lighter skin color and that variation in the ASIP gene may have been one of several factors contributing to reductions in pigmentation in some populations. Further study is needed to reveal how interactions between ASIP and several other genes, such as MC1R and P, predict human pigmentation.
肤色是社交互动的一个预测指标，也是多种癌症的风险因素，它由两种截然不同的黑色素形式导致，即颜色较深的真黑素和颜色较浅的褐黑素。较浅的色素褐黑素是刺鼠信号蛋白（ASIP）对α-黑素细胞刺激激素受体（MC1R）产生拮抗作用的产物。研究表明，ASIP基因3'非翻译区的一个单核苷酸多态性（SNP）与深色头发和眼睛有关；然而，关于其在个体肤色差异中的作用却知之甚少。在此，我们研究了234名非裔美国人中ASIP基因g.8818A>G SNP与通过反射测量法评估的肤色（M指数）之间的关系。进行方差分析（ANOVA）以评估ASIP基因型、年龄、个体血统和性别对肤色变化的影响。观察到ASIP基因型（F(2,236)=4.37，P=0.01）、血统（F(1,243)=37.2，P<0.001）和性别（F(1,244)=4.08，P=0.05）对M指数变化有显著影响。随后的分析揭示，ASIP基因型对非裔美国女性的M指数有强烈影响（P<0.001）。我们的研究表明，ASIP基因G>A多态性表现出显性效应，导致肤色变浅，并且ASIP基因的变异可能是导致某些人群色素沉着减少的几个因素之一。需要进一步研究以揭示ASIP与其他几个基因（如MC1R和P）之间的相互作用如何预测人类色素沉着。
