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The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans

Abstract

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 α-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.

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Acknowledgements

We are grateful to all individuals who participated in this study. We also thank Dale Young, Aisha Massac, and Cecily Jones for assistance in recruitment and data processing. Support for this work was provided by a Howard University, New Faculty Award (to R.A.K.) and the National Institutes of Health Office of Research on Minority Health (ORMH), the National Center for Research Resources (NCRR) and the National Human Genome Research Institute (NHGRI) (Grant ##GO2154 to M.D.S.).

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Correspondence to Rick A. Kittles.

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Bonilla, C., Boxill, L., Donald, S.A.M. et al. The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Hum Genet 116, 402–406 (2005). https://doi.org/10.1007/s00439-004-1251-2

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Keywords

  • Skin Color
  • Skin Pigmentation
  • Dark Hair
  • Individual Ancestry
  • Dark Skin Color