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 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.
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Until very recently, few direct studies to identify genes responsible for the normal range of human skin pigmentation have been reported, and all these studies investigated only known pigmentation-disorder genes in normal skin-color variation.
“However, until very recently, few direct studies to identify the genes responsible for the normal range of human skin pigmentation have been reported 13,[17][18][19][20][21][22][23][24][25][26] ; in addition, all these studies have investigated the role of only known pigmentation-disorder genes in normal skin-color variation.”
From A Genomewide Association Study of Skin Pigmentation in a South Asian Population (2007) · cites this paper as [18]
The effect size shown in Figure 5 for ASIP (0.24 MM) is estimated from 3.5 melanin units based on data in Bonilla et al.
“Similarly, the effect size shown in Figure 5 for ASIP (0.24 MM) is estimated from 3.5 melanin units based on data in Bonilla et al. [12].”
From Genetic Architecture of Skin and Eye Color in an African-European Admixed Population (2013) · cites this paper as [12]
Differences in skin pigmentation between sexes are likely population specific: whereas DermaSpectrometer M index measurements in this study show European males to have lighter skin pigmentation than European females, measurements in Island Melanesian, African Caribbeans, and African Americans have shown that in these populations males have darker skin pigmentation than females.
“Lastly, we emphasize that differences in skin pigmentation between sexes are likely population specific. Whereas DermaSpectrometer M index measurements in this study show European males to have lighter skin pigmentation than European females, DermaSpectrometer M index measurements of skin pigmentation in Island Melanesian, African Caribbeans, and African Americans have shown that in these populat”
From Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations (2012) · cites this paper as [47]
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- Authors
- Bonilla, C., Boxill, L.-A., Donald, S. A. M., Williams, T., Sylvester, N., Parra, E. J., Dios, S., Norton, H. L., Shriver, M. D., & Kittles, R. A.
- Affiliations
- Howard University (US)
- University of Toronto (CA)
- Pennsylvania State University (US)
- Corresponding author
- Kittles, Rick A.
- ORCID
- Venue
- Human Genetics
- Published
- 2005-02-22
- Volume
- 116
- Issue
- 5
- Pages
- 402-406
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- OpenAlex
- W2124735240
- Cited by
- 138
- References
- 23
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 7 · 2014: 10 · 2013: 4 · 2012: 8
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Race, Genetics, and Society
- Keywords
- ASIP, skin color, African Americans, melanin, pheomelanin, eumelanin, MC1R, 3' untranslated region, ancestry, sex differences, ancestral alleles
- MeSH terms
- Adult, Age Factors, Analysis of Variance, Black or African American, Female, Humans, Male, Sex Factors, Skin Pigmentation, Genetic Variation, Polymorphism, Single Nucleotide, Intercellular Signaling Peptides and Proteins, Agouti Signaling Protein
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