title: Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1.
abstract: BACKGROUND
  MYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim was to examine nine known polymorphisms in the MYG1 gene, to investigate their functionality, and to study their association with vitiligo susceptibility.
  
  
  METHODS
  Nine single nucleotide polymorphisms (SNPs) in the MYG1 locus were investigated by SNPlex assay and/or sequencing in vitiligo patients (n = 124) and controls (n = 325). MYG1 expression in skin biopsies was detected by quantitative-real time PCR (Q-RT-PCR) and polymorphisms were further analysed using luciferase and YFP reporters in the cell culture.
  
  
  RESULTS
  Control subjects with -119G promoter allele (rs1465073) exhibited significantly higher MYG1 mRNA levels than controls with -119C allele (P = 0.01). Higher activity of -119G promoter was confirmed by luciferase assay. Single marker association analysis showed that the -119G allele was more frequent in vitiligo patients (47.1%) compared to controls (39.3%, P < 0.05, OR 1.37, 95%CI 1.02-1.85). Analysis based on the stage of progression of the vitiligo revealed that the increased frequency of -119G allele occurred prevalently in the group of patients with active vitiligo (n = 86) compared to the control group (48.2% versus 39.3%, P < 0.05; OR 1.44, 95%CI 1.02-2.03). Additionally, we showed that glutamine in the fourth position (in Arg4Gln polymorphism) completely eliminated mitochondrial entrance of YFP-tagged Myg1 protein in cell culture. The analysis of available EST, cDNA and genomic DNA sequences revealed that Myg1 4Gln allele is remarkably present in human populations but is never detected in homozygous state according to the HapMap database.
  
  
  CONCLUSIONS
  Our study demonstrated that both MYG1 promoter polymorphism -119C/G and Arg4Gln polymorphism in the mitochondrial signal of Myg1 have a functional impact on the regulation of the MYG1 gene and promoter polymorphism (-119C/G) is related with suspectibility for actively progressing vitiligo.
authors.affiliation: Department of Physiology, University of Tartu, 19 Ravila Street, Tartu 50411, Estonia. maphilips@gmail.com
authors.forename: Mari-Anne
authors.initials: MA
authors.lastname: Philips
authors.forename: Külli
authors.initials: K
authors.lastname: Kingo
authors.forename: Maire
authors.initials: M
authors.lastname: Karelson
authors.forename: Ranno
authors.initials: R
authors.lastname: Rätsep
authors.forename: Eerik
authors.initials: E
authors.lastname: Aunin
authors.forename: Ene
authors.initials: E
authors.lastname: Reimann
authors.forename: Paula
authors.initials: P
authors.lastname: Reemann
authors.forename: Orm
authors.initials: O
authors.lastname: Porosaar
authors.forename: Jonas
authors.initials: J
authors.lastname: Vikeså
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
authors.forename: Helgi
authors.initials: H
authors.lastname: Silm
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005092:Exonucleases; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012880:Skin Pigmentation / Q000235:genetics; D014820:Vitiligo / Q000235:genetics*; D055815:Young Adult
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D004247:DNA; D005092:Exonucleases; C515548:MYG1 protein, human