1. ¹Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, China
2. ²The Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education, Hefei, China
3. ³Chinese National Human Genome Center at Shanghai, Shanghai, China
4. ⁴MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
5. ⁵Genome Institute of Singapore, Singapore

Correspondence: Professor Xue-Jun Zhang, Institute of Dermatology, Anhui Medical University, 69 Meishan Road, Hefei, Anhui 230032, PR China. E-mail: ayzxj@vip.sina.com; Dr Wei Huang, Chinese National Human Genome Center at Shanghai, 250 Bi Bo Road, Shanghai 201203, PR China. E-mail: huangwei@chgc.sh.cn

⁶These two authors contributed equally to this work.

Received 17 October 2006; Revised 21 January 2007; Accepted 31 January 2007; Published online 31 May 2007.

Abstract

Through a series of linkage analyses in a large Chinese family cohort of psoriasis, we previously identified and confirmed a non-HLA psoriasis linkage locus PSORS9 within a small region at 4q31.2–32.1. Within the critical region of the PSORS9 locus, IL-15 has been long recognized as a strong candidate gene for psoriasis. In this study, we investigated the association between IL-15 genetic polymorphisms and psoriasis in a large Chinese sample. Highly significant evidence for association was identified at a single-nucleotide polymorphism (SNP) (g.96516A T) within the 3'-untranslated region (UTR) of the IL-15 gene (P=0.00006, after correction for multiple testing). Haplotype analysis using the SNPs within the 3'UTR region also provided strong supporting evidence for association (P=0.00005), where we identified a haplotype of the 3'UTR region of IL-15 associated with increased risk to psoriasis (odds ratio=1.65). This association was also supported by the results of our expression activity analyses, where we demonstrated that the identified risk haplotype is associated with an increased activity of IL-15. Therefore, we provided early evidence for the important role of IL-15 genetic variants in the pathogenesis of psoriasis, probably by increasing interleukin production and inflammation in the lesions of psoriasis.