Variants in the 5q31 cytokine gene cluster are associated with psoriasis
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.
Steven J. Schrodi. "Variants in the 5q31 cytokine gene cluster are associated with psoriasis" Genes and Immunity (2007).
Available at: http://works.bepress.com/steve_schrodi/28