title: 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.
authors.affiliation: Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, 494 Tzagournis Medical Research Facility, 420 W. 12th Avenue, Columbus, OH 43210, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bonilla
authors.forename: Lesley-Anne
authors.initials: LA
authors.lastname: Boxill
authors.forename: Stacey Ann Mc
authors.initials: SA
authors.lastname: Donald
authors.forename: Tyisha
authors.initials: T
authors.lastname: Williams
authors.forename: Nadeje
authors.initials: N
authors.lastname: Sylvester
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Parra
authors.forename: Sonia
authors.initials: S
authors.lastname: Dios
authors.forename: Heather L
authors.initials: HL
authors.lastname: Norton
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Rick A
authors.initials: RA
authors.lastname: Kittles
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000367:Age Factors; D054366:Agouti Signaling Protein; D000704:Analysis of Variance; D005260:Female; D014644:Genetic Variation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D012880:Skin Pigmentation / Q000235:genetics*
chemical_list: D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins
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