title: Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians.
abstract: Human melanocortin 1 receptor (MC1R) is a seven transmembrane G-coupled protein receptor that upregulates the cAMP pathway. Several functional variants of MC1R that show an impaired ability to activate the cAMP pathway are strongly associated with fair skin and red hair in Europeans and European descendants. The sequence variations of the MC1R gene were repeatedly investigated against worldwide populations; however, there was no evidence that functional variant of MC1R exists in non-European descendants. We report the presence of novel functional variants of MC1R with Asian origins. Three novel variants of MC1R, Phe147Delta, Thr157Ile, and Pro159Thr, were identified in our screening for the sequence variations of the MC1R gene against 995 individuals from 30 Asian and Oceanian populations; there was a single case for the Pro159Thr variant allele and two instances of Phe147Delta and Thr157Ile variant alleles. Our pharmacological assay revealed that Phe147Delta, Thr157Ile, and Pro159Thr variant showed similar or more dramatically impaired activities in comparison with Arg151Cys, which is a major functional variant of MC1R in Europeans. These functional variant alleles were geographically localized in relatively high latitudes, which suggest that the adaptation to ambient UV light intensity may play an important role in shaping the geographical distribution of MC1R alleles in Asia and Oceania.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 1130033, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Augustinus
authors.initials: A
authors.lastname: Soemantri
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.forename: Bumbein
authors.initials: B
authors.lastname: Dashnyam
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Ohtsuka
authors.forename: Phaibool
authors.initials: P
authors.lastname: Duanchang
authors.forename: Mohd Nizam
authors.initials: MN
authors.lastname: Isa
authors.forename: Wannapa
authors.initials: W
authors.lastname: Settheetham-Ishida
authors.forename: Shinji
authors.initials: S
authors.lastname: Harihara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000818:Animals; D001210:Asia, Southeastern; D044466:Asian People / Q000235:genetics*; D019556:COS Cells; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000096:biosynthesis; D014644:Genetic Variation; D006200:Hair Color / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D010641:Phenotype; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics* / Q000378:metabolism; D012880:Skin Pigmentation / Q000235:genetics; D014162:Transfection
chemical_list: D044102:Receptor, Melanocortin, Type 1; D000242:Cyclic AMP