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

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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Authors and Affiliations

1. Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, 494 Tzagournis Medical Research Facility, 420 W. 12th Avenue, Columbus, OH, 43210, USA
   Carolina Bonilla & Rick A. Kittles
2. National Human Genome Center, Howard University, Washington, DC, 20060, USA
   Carolina Bonilla, Lesley-Anne Boxill, Stacey Ann Mc Donald, Tyisha Williams, Nadeje Sylvester & Rick A. Kittles
3. Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, LSL 1C6, Canada
   Esteban J. Parra
4. Department of Anthropology, The Pennsylvania State University, University Park, PA, 16802, USA
   Sonia Dios, Heather L. Norton & Mark D. Shriver

Authors

1. Carolina Bonilla
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2. Lesley-Anne Boxill
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3. Stacey Ann Mc Donald
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4. Tyisha Williams
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5. Nadeje Sylvester
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6. Esteban J. Parra
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7. Sonia Dios
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8. Heather L. Norton
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9. Mark D. Shriver
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10. Rick A. Kittles
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Correspondence toRick A. Kittles.

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Bonilla, C., Boxill, LA., 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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• Received: 01 September 2004
• Accepted: 14 December 2004
• Published: 22 February 2005
• Issue Date: April 2005
• DOI: https://doi.org/10.1007/s00439-004-1251-2

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