Polymorphisms in interleukin-15 gene on chromosome 4q31.2 are associated with psoriasis vulgaris in Chinese population

J Invest Dermatol. 2007 Nov;127(11):2544-51. doi: 10.1038/sj.jid.5700896. Epub 2007 May 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • China
  • Chromosomes, Human, Pair 4 / genetics*
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Interleukin-15 / genetics*
  • Interleukin-15 / metabolism
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Psoriasis / ethnology
  • Psoriasis / genetics*
  • Psoriasis / metabolism

Substances

  • Interleukin-15