title: Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population.
abstract: 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.
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas-Houston, 77030, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Akey
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Xiong
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: M D
authors.initials: MD
authors.lastname: Shriver
authors.forename: L
authors.initials: L
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002681:China; D004247:DNA / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018043:Receptors, Corticotropin / Q000235:genetics*; D044101:Receptors, Melanocortin; D012880:Skin Pigmentation / Q000235:genetics*; D018609:Tibet / Q000208:ethnology
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D004247:DNA