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Human Molecular Genetics Advance Access originally published online on July 9, 2008
Human Molecular Genetics 2008 17(19):2978-2985; doi:10.1093/hmg/ddn196
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The 5q31 variants associated with psoriasis and Crohn's disease are distinct

Yonghong Li1,*, Monica Chang1, Steven J. Schrodi1, Kristina P. Callis-Duffin2, Nori Matsunami3, Daniel Civello1,{dagger}, Nam Bui1, Joseph J. Catanese1, Mark F. Leppert3,4, Gerald G. Krueger2 and Ann B. Begovich1,{ddagger}

1 Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA 2 Department of Dermatology 3 Department of Human Genetics, University of Utah, Salt Lake City, UT 84132, USA 4 LineaGen Research Corporation, Salt Lake City, UT 84101, USA

* To whom correspondence should be addressed. Tel: +1 5107496283; Fax: +1 5107496200; Email: yonghong.li{at}celera.com

Received March 26, 2008; Accepted July 7, 2008

Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B and IL23R, but other genetic risk factors also exist. We recently reported three psoriasis-associated single nucleotide polymorphisms (SNPs) in the 5q31 locus, a region of high linkage disequilibrium laden with inflammatory pathway genes. The aim of this study was to assess whether other variants in the 5q31 region are causal to these SNPs or make independent contributions to psoriasis risk by genotyping a comprehensive set of tagging SNPs in a 725 kb region bounded by IL3 and IL4 and testing for disease association. Ninety SNPs, capturing 86.4% of the genetic diversity, were tested in one case–control sample set (467 cases/460 controls) and significant markers (Pallelic < 0.05) (n = 9) were then tested in two other sample sets (981 cases/925 controls). All nine SNPs were significant in a meta-analysis of the combined sample sets. Pair-wise conditional association tests showed rs1800925, an intergenic SNP located just upstream of IL13 (Mantel–Haenszel Pcombined = 1.5 x 10–4, OR = 0.77 [0.67–0.88]), could account for observed significant association of all but one other SNP, rs11568506 in SLC22A4 [Mantel–Haenszel Pcombined = 0.043, OR = 0.68 (0.47–0.99)]. Haplotype analysis of these two SNPs showed increased significance for the two common haplotypes (rs11568506–rs1800925: GC, Pcombined = 5.67 x 10–6, OR = 1.37; GT, Pcombined = 6.01 x 10–5, OR = 0.75; global haplotype P = 8.93 x 10–5). Several 5q31-region SNPs strongly associated with Crohn's disease (CD) in the recent WTCCC study were not significant in the psoriasis sample sets tested here. These results identify the most significant 5q31 risk variants for psoriasis and suggest that distinct 5q31 variants contribute to CD and psoriasis risk.

{dagger} Present address: Genomic Health, Inc., 301 Penobscot Dr., Redwood City, CA 95063, USA.

{ddagger} Present address: Roche Molecular Diagnostics, 4300 Hacienda Dr., Pleasanton, CA 94588, USA.


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