title: Identification of a possible susceptibility locus for UVB-induced skin tanning phenotype in Korean females using genomewide association study.
abstract: A two-stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)-induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs that were highly associated with tanning ability. To confirm these associations, we genotyped the SNPs in an independent replication study (112 Korean females). We found that a novel SNP in the intron of the WW domain-containing oxidoreductase (WWOX) gene yielded significant replicated associations with skin tanning ability (P-value = 1.16 × 10(-4) ). To understand the functional consequences of this locus located in the non-coding region, we investigated the role of WWOX in human melanocytes using a recombinant adenovirus expressing a microRNA specific for WWOX. Inhibition of WWOX expression significantly increased the expression and activity of tyrosinase in human melanocytes. Taken together, our results suggest that genetic variants in the intronic region of WWOX could be determinants in the UV-induced tanning ability of Korean females. WWOX represents a new candidate gene to evaluate the molecular basis of the UV-induced tanning ability in individuals.
authors.affiliation: LG Household and Healthcare, Daejeon, Korea.
authors.forename: Taek-Jong
authors.initials: TJ
authors.lastname: Kwak
authors.affiliation: LG Household and Healthcare, Daejeon, Korea.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Theragen-Etex Bio Institute, Advanced Institute of Convergence Technology, Kwanggyo Technovalley, Suwon, Korea.
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Shin
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Theragen-Etex Bio Institute, Advanced Institute of Convergence Technology, Kwanggyo Technovalley, Suwon, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Lim
authors.affiliation: LG Household and Healthcare, Daejeon, Korea.
authors.forename: Sang-Hwha
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Min-Geol
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Yoon
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Chang-Deok
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Dermapro Skin Research Center, Seoul, Korea.
authors.forename: Jae Sook
authors.initials: JS
authors.lastname: Koh
authors.affiliation: Dermapro Skin Research Center, Seoul, Korea.
authors.forename: Young Kyoung
authors.initials: YK
authors.lastname: Seo
authors.affiliation: LG Household and Healthcare, Daejeon, Korea.
authors.forename: Min-Youl
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
mesh_terms: D000328:Adult; D044466:Asian People; D002478:Cells, Cultured; D005260:Female; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007438:Introns; D008544:Melanocytes / Q000201:enzymology / Q000528:radiation effects; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D056910:Republic of Korea; D012867:Skin / Q000201:enzymology* / Q000528:radiation effects*; D012880:Skin Pigmentation / Q000235:genetics* / Q000502:physiology / Q000528:radiation effects*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D035683:MicroRNAs; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: UVB; WW domain-containing oxidoreductase; genomewide association study; phenotype; tanning