title: Genetic variants of the DDR1 gene are associated with vitiligo in two independent Brazilian population samples.
abstract: Vitiligo is a chronic disease characterized by macules devoid of melanin and identifiable melanocytes. Adhesion of melanocytes to the basement membrane by integrin CCN3 is mediated through collagen IV receptor DDR1. We hypothesize that genetic variants of the DDR1 gene are associated with the occurrence of vitiligo. To test this hypothesis, we genotyped 10 DDR1 tag single-nucleotide polymorphisms (SNPs) in 212 trios composed of an affected child and both parents. Associated markers were then genotyped in 134 independent, unrelated individuals with vitiligo and 134 unrelated controls. Allele T of tag SNP rs4618569 was associated with an increased risk for vitiligo in the family trios (P=0.002, odds ratio (OR)=5.27; 95% confidence interval (CI)=1.59-17.40), whereas allele C of tag SNP rs2267641 was associated with an increased risk for vitiligo in both family-based and case-control populations (P=0.01, OR=3.47; 95% CI=1.22-9.17; P=0.04, OR=6.00; 95% CI=1.73-52.33, respectively). The best evidence for association in the trios was obtained for a haplotype composed of risk alleles of markers rs4618569 and rs2267641 (P=0.0006). There was an age-dependent enrichment of rs4618569 T allele and rs2267641 C allele in early-onset affected individuals. In conclusion, we propose DDR1 as a susceptibility gene for vitiligo, possibly implicating a defective cell adhesion in vitiligo pathogenesis.
authors.affiliation: Department of Dermatology, Santa Casa de Misericórdia Hospital, Pontifical Catholic University of Paraná, Curitiba, Paraná, Brazil.
authors.forename: Caio Cesar
authors.initials: CC
authors.lastname: Silva de Castro
authors.forename: Liliane Machado
authors.initials: LM
authors.lastname: do Nascimento
authors.forename: Gaby
authors.initials: G
authors.lastname: Walker
authors.forename: Renata Iani
authors.initials: RI
authors.lastname: Werneck
authors.forename: Everson
authors.initials: E
authors.lastname: Nogoceke
authors.forename: Marcelo Távora
authors.initials: MT
authors.lastname: Mira
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics; D002648:Child; D000070819:Discoidin Domain Receptor 1; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors; D014820:Vitiligo / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases