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

Genes & Immunity volume 9, pages 176–181 (2008)Cite this article

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; Pcomb: 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; Pcomb=1.88E−04) and a less common, protective haplotype TTT (joint allelic OR=0.74; Pcomb=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.

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Acknowledgements

We are grateful to all the individuals with psoriasis and control subjects for participation in this study. We thank J Sninsky and T White for their comments on the manuscript, scientific advice and support. We also thank the members of the Celera High Throughput and Computational Biology groups, C Rowland for statistical advice and support, S Prescott, M Paul and everyone at Lineagen and E Beasley and L McAllister for help with this project. This study was supported in part by a Public Health Services research grant to the Huntsman General Clinical Research Center at the University of Utah, by National Center for Research Resources Grant M01-RR00064 and by generous gifts from the WM Keck Foundation and from the George S and Delores Dore Eccles Foundation.

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Author notes

  1. M Cargill

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

Authors and Affiliations

  1. Celera, Alameda, CA, USA

    M Chang, Y Li, C Yan, V E Garcia, M Cargill, D Civello, N Bui, J J Catanese, A B Begovich & S J Schrodi

  2. Department of Dermatology, University of Utah, Salt Lake City, UT, USA

    K P Callis-Duffin & G G Krueger

  3. Department of Human Genetics, University of Utah, Salt Lake City, UT, USA

    N Matsunami & M F Leppert

  4. LineaGen Research Corporation, Salt Lake City, UT, USA

    M F Leppert

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  1. M Chang
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Corresponding author

Correspondence to A B Begovich.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Chang, M., Li, Y., Yan, C. et al. Variants in the 5q31 cytokine gene cluster are associated with psoriasis. Genes Immun 9, 176–181 (2008). https://doi.org/10.1038/sj.gene.6364451

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