title: Polymorphisms in Toll-like receptor genes are associated with vitiligo.
abstract: BACKGROUND
  The members of Toll-like receptor (TLR) family are responsible for recognizing various molecular patterns associated with pathogens. Their expression is not confined to immune cells and have been detected in skin cells such as keratinocytes and melanocytes. As part of a generated response to pathogens, TLRs are involved in inducing inflammatory mediators to combat these threats. It is therefore not surprising that TLRs have been implicated in inflammatory skin diseases, including atopic dermatitis and psoriasis. Likewise, as key players in autoimmunity, they have been associated with a number of autoimmune diseases. Based on this, the role of TLRs in vitiligo could be suspected, but is yet to be clearly established.
  
  
  METHODS
  In order to conduct a genetic association analysis, 30 SNPs were selected from TLR1-TLR8 and TLR10 regions to be genotyped in Estonian case-control cohort consisting of 139 vitiligo patients and 307 healthy control individuals. The patients were further analyzed in subgroups based on sex, age of onset, occurrence of vitiligo among relatives, extent of depigmented areas, vitiligo progression activity, appearance of Köbner's phenomenon, existence of halo naevi, and incidence of spontaneous repigmentation.
  
  
  RESULTS
  The most notable finding came with SNP rs179020 situated in TLR7 gene, that was associated in entire vitiligo (Padj = 0.0065) and also several subgroup analyses. Other single marker and haplotype analyses pointed to TLR3, TLR4, and TLR10 genes.
  
  
  CONCLUSIONS
  This study investigated the genetic regions of nine TLR genes in relation to vitiligo susceptibility. The main results were the associations of TLR7 SNPs with vitiligo, while several other associations were obtained from the remaining TLR gene regions. This suggests that in addition to other inflammatory skin diseases, TLRs affect the development of vitiligo, thus making them interesting targets for future research.
authors.affiliation: Department of Dermatology, University of Tartu Tartu, Estonia ; Centre of Excellence for Translational Medicine, University of Tartu Tartu, Estonia.
authors.forename: Tanel
authors.initials: T
authors.lastname: Traks
authors.affiliation: Department of Dermatology, University of Tartu Tartu, Estonia ; Clinic of Dermatology, Tartu University Hospital Tartu, Estonia.
authors.forename: Maris
authors.initials: M
authors.lastname: Keermann
authors.affiliation: Department of Dermatology, University of Tartu Tartu, Estonia ; Clinic of Dermatology, Tartu University Hospital Tartu, Estonia.
authors.forename: Maire
authors.initials: M
authors.lastname: Karelson
authors.affiliation: Department of Physiology, University of Tartu Tartu, Estonia.
authors.forename: Ranno
authors.initials: R
authors.lastname: Rätsep
authors.affiliation: Department of Pathophysiology, University of Tartu Tartu, Estonia ; Department of Reproductive Biology, Estonian University of Life Sciences Tartu, Estonia.
authors.forename: Ene
authors.initials: E
authors.lastname: Reimann
authors.affiliation: Department of Dermatology, University of Tartu Tartu, Estonia ; Clinic of Dermatology, Tartu University Hospital Tartu, Estonia.
authors.forename: Helgi
authors.initials: H
authors.lastname: Silm
authors.affiliation: Centre of Excellence for Translational Medicine, University of Tartu Tartu, Estonia ; Department of Physiology, University of Tartu Tartu, Estonia.
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
authors.affiliation: Centre of Excellence for Translational Medicine, University of Tartu Tartu, Estonia ; Department of Pathophysiology, University of Tartu Tartu, Estonia ; Department of Reproductive Biology, Estonian University of Life Sciences Tartu, Estonia.
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.affiliation: Department of Dermatology, University of Tartu Tartu, Estonia ; Clinic of Dermatology, Tartu University Hospital Tartu, Estonia.
authors.forename: Külli
authors.initials: K
authors.lastname: Kingo
keywords: SNP; Toll-like receptor; autoimmune; genetic association study; vitiligo