Polymorphisms of the IL12B and IL23R genes are associated with psoriasis

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.