title: Polymorphisms of the IL12B and IL23R genes are associated with psoriasis.
abstract: Psoriasis is a common inflammatory and hyperproliferative skin disease with a multifactorial genetic basis. A recent study reported that psoriasis was associated with the IL12B haplotype rs3212227 (3'-untranslated region)-rs6887695 (60 kb, 5') and the IL23R haplotype rs7530511 (L310P)-rs11209026 (Q381R). We examined these four single-nucleotide polymorphisms (SNPs) for association with psoriasis in two groups of North American and German Caucasians: (1) 1,810 cases and 2,522 controls; and (2) 509 pedigrees. Both IL12B markers showed highly significant association with psoriasis in the case-control (rs3212227, odds ratio (OR)=1.62, P=1.7 x 10(-15); rs6887695, OR=1.49, P=2.7 x 10(-15)) and in the family-based analysis (rs3212227, P=2.2 x 10(-3); rs6887695, P=1.7 x 10(-3)). The IL23R SNPs also showed significant association in the cases and controls (rs7530511, OR=1.22, P=3.9 x 10(-3); rs11209026, OR=1.40, P=3.8 x 10(-4)). For both genes, common risk haplotypes were identified whose statistical significance approached (IL23R) or exceeded (IL12B) genome-wide criteria. We found no statistical evidence for interactions of these haplotypes with HLA-Cw6. Our results confirm associations between IL12B and IL23R and psoriasis in Caucasians, and provide a genetic basis for the clinical association between psoriasis and Crohn's disease.
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0932, USA.
authors.forename: Rajan P
authors.initials: RP
authors.lastname: Nair
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruether
authors.forename: Philip E
authors.initials: PE
authors.lastname: Stuart
authors.forename: Stefan
authors.initials: S
authors.lastname: Jenisch
authors.forename: Trilokraj
authors.initials: T
authors.lastname: Tejasvi
authors.forename: Ravi
authors.initials: R
authors.lastname: Hiremagalore
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
authors.forename: Henry W
authors.initials: HW
authors.lastname: Lim
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
authors.forename: Enno
authors.initials: E
authors.lastname: Christophers
authors.forename: James T
authors.initials: JT
authors.lastname: Elder
authors.forename: Michael
authors.initials: M
authors.lastname: Weichenthal
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*
chemical_list: C515500:IL23R protein, human; D053762:Interleukin-12 Subunit p40; D018123:Receptors, Interleukin