Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population

• Published in: Human genetics 2001-06, Vol.108 (6), p.516-520
• Main Authors: AKEY, Joshua M, HONG WANG, MOMIAO XIONG, HONG WU, WEIDA LIU, SHRIVER, Mark D, LI JIN
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Biological and medical sciences; Carrier Proteins - genetics; Child; China; DNA - genetics; Epistasis, Genetic; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Human; Humans; Male; Membrane Proteins - genetics; Membrane Transport Proteins; Phenotype; Polymorphism, Single Nucleotide; Population genetics, reproduction patterns; Receptors, Corticotropin - genetics; Receptors, Melanocortin; Skin Pigmentation - genetics; Tibet - ethnology
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390100524

The melanocortin-1 receptor (MC1R) and P gene product are two important components of the human pigmentary system that have been shown to be associated with red hair/fair skin and cause type II oculocutaneous albinism, respectively. However, their contribution to inter-individual variation at the population level is not well defined. To this end, we genotyped 3 single nucleotide polymorphisms (SNPs) in the MC1R gene (Arg67Gln, Gln163Arg, Val92Met) and 2 SNPs in the P gene (IVS 13-15 and Gly780Gly) in 184 randomly ascertained Tibetan subjects, whose skin color was measured as a quantitative trait by reflective spectroscopy. Single locus analyses failed to demonstrate an association between any of the 5 SNPs and skin pigmentation. However, when an epistatic model was applied to the data, a significant gene-gene interaction was identified between Val92Met in MCIR and IVS13-15 in the P gene (F=2.43; P=0.0105). We also discuss the possible mechanisms of how gene interactions arise in signal transduction pathways.