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 × 10⁻¹⁵; rs6887695, OR=1.49, P=2.7 × 10⁻¹⁵) and in the family-based analysis (rs3212227, P=2.2 × 10⁻³; rs6887695, P=1.7 × 10⁻³). The IL23R SNPs also showed significant association in the cases and controls (rs7530511, OR=1.22, P=3.9 × 10⁻³; rs11209026, OR=1.40, P=3.8 × 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.

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