The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans.
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.
Bonilla
Carolina
C
Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, 494 Tzagournis Medical Research Facility, 420 W. 12th Avenue, Columbus, OH 43210, USA.
Boxill
Lesley-Anne
LA
Donald
Stacey Ann Mc
SA
Williams
Tyisha
T
Sylvester
Nadeje
N
Parra
Esteban J
EJ
Dios
Sonia
S
Norton
Heather L
HL
Shriver
Mark D
MD
Kittles
Rick A
RA
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*
D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins
Annu Rev Genet. 2003;37:67-90
14616056
Nature. 1994 Oct 27;371(6500):799-802
7935841
Pigment Cell Res. 2002 Apr;15(2):112-8
11936268
Am J Hum Genet. 2003 Jun;72(6):1492-1504
12817591
Am J Phys Anthropol. 2000 May;112(1):17-27
10766940
Hum Genet. 2004 Jun;115(1):57-68
15118905
Pigment Cell Res. 1994 Aug;7(4):217-21
7855066
Nat Rev Genet. 2004 Aug;5(8):611-8
15266343
Hum Mol Genet. 1995 Feb;4(2):223-30
7757071
Pigment Cell Res. 2002 Feb;15(1):10-8
11837451
Pigment Cell Res. 2004 Apr;17(2):185-7
15016309
Obes Res. 2002 Jun;10(6):447-52
12055320
Hum Genomics. 2003 Nov;1(1):52-62
15601533
Am J Phys Anthropol. 1986 Aug;70(4):433-41
3766713
Hum Genet. 2003 Apr;112(4):387-99
12579416
J Med Genet. 2004 Nov;41(11):e116
15520398
Hum Genet. 2002 Jun;110(6):553-60
12107441
Pigment Cell Res. 2003 Feb;16(1):65-71
12519127
Am J Hum Genet. 2002 Mar;70(3):770-5
11833005
J Invest Dermatol. 1997 Jun;108(6):838-42
9182807