title: Association analysis of genes of the IL19 cluster and their receptors in vitiligo patients.
abstract: The aim of the present study was to explore whether the genes encoding interleukin (IL) 19, IL-20, IL-24 and 2 chains of the IL-20 receptor type I (IL-20-RI), IL-20RA and IL-20RB, located on chromosomes 1q32, 6q22–23 and 3q22, respectively, are associated with vitiligo. The study involved 76 patients with vitiligo and 236 unrelated healthy volunteers. Genomic DNA was extracted from the whole blood and the frequencies of 20 single nucleotide polymorphisms were analysed by tetraprimer amplification refractory mutation system polymerase chain reaction. The minor allele of IL19 rs2243188 was significantly increased in vitiligo patients compared to controls (53.3 vs. 28.6%, adjusted p < 0.0001). The haplotype analysis revealed associations of 2 IL19/IL20 extended haplotypes (AACGTAA and ACCGTAA) and 2 IL20RB haplotypes (AGTA and AGGA) with vitiligo, remaining significant after correction for multiple testing. The A-to-C exchange at position IL19 rs2243188 leads to the loss of a nuclear receptor subfamily 2 factor binding site that is thought to influence mouse hippocampal development and neuronal differentiation. The third position of the IL20RB haplotypes is taken by rs747842 that induces the loss of the interferon regulatory factor 4 binding site that has an important role in the regulation of innate and adaptive immunity and in the signalling of pigmentation as well. In conclusion, the present study describes first-time associations between polymorphisms of genes of the IL19 cluster and their receptors and vitiligo, indicative of the part of IL19 and its receptor gene IL20RB in disease pathogenesis.
authors.affiliation: Department of Dermatology and Venereology, University of Tartu, Tartu, Estonia.
authors.forename: Külli
authors.initials: K
authors.lastname: Kingo
authors.forename: Ene
authors.initials: E
authors.lastname: Reimann
authors.forename: Maire
authors.initials: M
authors.lastname: Karelson
authors.forename: Ranno
authors.initials: R
authors.lastname: Rätsep
authors.forename: Kristi
authors.initials: K
authors.lastname: Raud
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; D000483:Alleles; D002878:Chromosomes, Human, Pair 1; D002893:Chromosomes, Human, Pair 3; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D014820:Vitiligo / Q000235:genetics*; D055815:Young Adult; D000099180:Interleukin-24
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin; D000099180:Interleukin-24; C421250:IL19 protein, human; C492510:interleukin-20 receptor; C422042:interleukin 20