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.

Access this article

Log in via an institution

Subscribe and save

• Get 10 units per month
• Download Article/Chapter or eBook
• 1 Unit = 1 Article or 1 Chapter
• Cancel anytime Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

• Alaluf S, Atkins D, Barrett K, Blount M, Carter N, Heath A (2002) Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin. Pigment Cell Res 15:112–118
  Google Scholar
• Bonilla C (2003) Admixture in three Hispanic populations: ancestry proportions, population structure, and gene mapping. PhD dissertation, The Pennsylvania State University, Pennsylvania
  Google Scholar
• Bonilla C, Shriver M, Parra E, Jones A, Fernandez J (2004) Ancestral proportions and their association with skin pigmentation and bone mineral density in Puerto Rican women from New York city. Hum Genet 115:57–68
  Google Scholar
• Halder I, Shriver M (2003) Measuring and using admixture to study the genetics of complex diseases. Hum Genomics 1:52–62
  Google Scholar
• Hanis C, Chakraborty R, Ferrell R, Schull W (1986) Individual admixture estimates: disease associations and individual risk of diabetes and gallbladder disease among Mexican-Americans in Starr County, Texas. Am J Phys Anthropol 70:433–441
  Google Scholar
• Hoggart C, Parra E, Shriver M, Bonilla C, Kittles R, Clayton D, McKeigue P (2003) Control of confounding of genetic associations in stratified populations. Am J Hum Genet 72:1492–1504
  Article Google Scholar
• Hunt G, Donatien P, Lunec J, Todd C, Kyne S, Thody A (1994) Cultured human melanocytes respond to MSH peptides and ACTH. Pigment Cell Res 7:217–221
  Google Scholar
• Kanetsky P, Swoyer J, Panossian S, Holmes R, Guerry D, Rebbeck T (2002) A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 70:770–775
  Google Scholar
• Kittles R, Chen W, Panguluri R, Ahaghotu C, Jackson A, Ademabowo C, Griffin R, Williams T, Ukoli F, Adams-Campbell L, Kwagyan J, Isaacs W, Freeman V, Dunston G (2002) CYP3A4-V and prostate cancer in African Americans: causal or confounding association because of population stratification? Hum Genet 110:553–560
  Google Scholar
• Lu D, Willard D, Patel I, Kadwell S, Overton L, Kost T, Luther M, Chen W, Woychik R, Wilkinson W, Cone R (1994) Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371:799–802
  Article CAS PubMed Google Scholar
• Parra E, Hoggart C, Bonilla C, Dios S, Norris J, Marshall J, Hamman R, Ferrell R, McKeigue P, Shriver M (2004) Relation of type 2 diabetes to individual admixture and candidate gene polymorphisms in the Hispanic American population of San Luis Valley, Colorado. J Med Genet 41:e116
  Google Scholar
• Rees J (2003) Genetics of hair and skin color. Annu Rev Genet 37:67–90
  Google Scholar
• Robins A (1991) Biological perspectives on human pigmentation. Cambridge University Press, Cambridge
  Google Scholar
• Shriver M, Kittles R (2004) Opinion: genetic ancestry and the search for personalized genetic histories. Nat Rev Genet 5:611–618
  Google Scholar
• Shriver MD, Parra EJ (2000) Comparison of narrow-band reflectance spectroscopy and tristimulus colorimetry for measurements of skin and hair color in persons of different biological ancestry. Am J Phys Anthropol 112:17-27
  Google Scholar
• Shriver M, Parra E, Dios S, Bonilla C, Norton H, Jovel C, Pfaff C, Jones C, Massac A, Cameron N, Baron A, Jackson T, Argyropoulos G, Jin L, Hoggart C, McKeigue P, Kittles R (2003) Skin pigmentation, biogeographical ancestry and admixture mapping. Hum Genet 112:387–399
  PubMed Google Scholar
• Suzuki I, Tada A, Ollmann M, Barsh G, Im S, Lamoreux M, Hearing V, Nordlund J, Abdel-Malek Z (1997) Agouti signaling protein inhibits melanogenesis and the response of human melanocytes to alpha-melanotropin. J Invest Dermatol 108:838–842
  Google Scholar
• Voisey J, Van Daal A (2002) Agouti: from mouse to man, from skin to fat. Pigment Cell Res 15:10–18
  Google Scholar
• Voisey J, Imbeault P, Hutley L, Prins J, Van Daal A (2002) Body mass index-related human adipocyte agouti expression is sex-specific but not depot-specific. Obes Res 10:447–452
  Google Scholar
• Voisey J, Kelly G, Van Daal A (2003) Agouti signal protein regulation in human melanoma cells. Pigment Cell Res 16:65–71
  Google Scholar
• Wilson B, Ollmann M, Kang L, Stoffel M, Bell G, Barsh G (1995) Structure and function of ASP, the human homolog of the mouse agouti gene. Hum Mol Genet 4:223–230
  Google Scholar
• Zeigler-Johnson C, Panossian S, Gueye S, Jalloh M, Ofori-Adjei D, Kanetsky P (2004) Population differences in the frequency of the agouti signaling protein g.8188A>G polymorphism. Pigment Cell Res 17:185–187
  Google Scholar

Download references

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.).

Author information

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

Corresponding author

Correspondence toRick A. Kittles.

Rights and permissions

About this article

Cite this article

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

Download citation

• 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

Keywords