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 725kb region bounded by IL3 and IL4 and testing for disease association. Ninety SNPs were tested in one case-control sample set (467 cases and 460 controls), and significant markers (P<0.05) (N=9) were then tested in two other sample sets (981 cases and 925 controls). All nine SNPs were significant in a meta-analysis of the combined sample sets. Pairwise conditional association tests of the SNPs genotyped in all three sample sets showed that the original IL13 SNP, rs1800925, (Mantel-Haenszel Pcombined=1.5x10-4, 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=5.67x10-6, OR=1.37; GT, Pcombined=6.01x10-5, OR=0.75; global haplotype P=8.93x10-5). Interestingly, several 5q31-region SNPs strongly associated with Crohn’s disease in the recent Wellcome Trust Case Control Consortium 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 variants contribute to CD and psoriasis risk.
Available at: http://works.bepress.com/steve_schrodi/35/