Variants in the 5q31 cytokine gene cluster are associated with psoriasis

Steven J. Schrodi, Celera, Inc

Abstract

Following a staged functional SNP scan involving 25,215 markers, we report the findings of three IL13-linked SNPs (rs1800925, rs20541, rs848) associated with psoriasis. Three case-control sample sets were used, comprising a total of 1,446 patients and 1,432 controls. Although the susceptibility effects at these IL13 SNPs were modest (joint allelic ORrs1800925=0.76, joint allelic ORrs20541=0.78, joint allelic ORrs848=0.78) (allelic Prs1800925=3.7E-04, allelic Prs20541=0.0013, allelic Prs848=0.0017), the association patterns were consistent across the sample sets, with moderate odds ratios ranging from 0.73-0.83 (the minor allele is protective against psoriasis susceptibility). Haplotype analyses performed indicate one common, susceptible haplotype CCG (P=1.9E-04) and a less common, haplotype TTT conferring protection against psoriasis (P=7.0E-04). Lastly, we used genotype information from the known predisposing loci HLA-C, IL12B and IL23R, combined with these IL13 data to generate a psoriasis risk plot, showing a 11-fold variation between susceptible and protective multi-locus genotype combinations. Residing on chromosome 5q31, IL13 is an important T-cell derived cytokine regulating a number of inflammatory responses. While these results are encouraging, additional genetic and functional studies are needed to fully dissect these IL13 associations within this cytokine-rich area of the genome as polymorphisms in closely-linked candidate genes such as IRF1, IL5 or IL4 may be driving these results through linkage disequilibrium. We hope that this report will motivate such studies.