1. ¹Celera, Alameda, CA, USA
2. ²Department of Dermatology, University of Utah, Salt Lake City, UT, USA
3. ³Department of Human Genetics, University of Utah, Salt Lake City, UT, USA
4. ⁴LineaGen Research Corporation, Salt Lake City, UT, USA

Correspondence: Dr AB Begovich, Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA. E-mail: ann.begovich@celera.com

⁵Current address: Navigenics, Redwood Shores, CA, USA.

Received 8 October 2007; Revised 12 November 2007; Accepted 13 November 2007; Published online 13 December 2007.

Abstract

A multitiered genetic association study of 25 215 single-nucleotide polymorphisms (SNPs) in three case–control sample sets (1446 patients and 1432 controls) identified three IL13-linked SNPs (rs1800925, rs20541 and rs848) associated with psoriasis. Although the susceptibility effects at these SNPs were modest (joint allelic odds ratios (ORs): 0.76 to 0.78; P_comb: 1.3E-03 to 2.50E-04), the association patterns were consistent across the sample sets, with the minor alleles being protective. Haplotype analyses identified one common, susceptible haplotype CCG (joint allelic OR=1.27; P_comb=1.88E-04) and a less common, protective haplotype TTT (joint allelic OR=0.74; P_comb=7.05E-04). In combination with the other known genetic risk factors, HLA-C, IL12B and IL23R, the variants reported here generate an 11-fold psoriasis-risk differential. Residing in the 5q31 cytokine gene cluster, IL13 encodes an important T-cell-derived cytokine that regulates cell-mediated immunity. These results provide the foundation for additional studies required to fully dissect the associations within this cytokine-rich genomic region, as polymorphisms in closely linked candidate genes, such as IRF1, IL5 or IL4, may be driving these results through linkage disequilibrium.