Polymorphisms in interleukin-15 gene on chromosome 4q31.2 are associated with psoriasis vulgaris in Chinese population.
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.
Zhang
Xue-Jun
XJ
Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, China. ayzxj@vip.sina.com
Yan
Kai-Lin
KL
Wang
Zhi-Min
ZM
Yang
Sen
S
Zhang
Guo-Long
GL
Fan
Xing
X
Xiao
Feng-Li
FL
Gao
Min
M
Cui
Yong
Y
Wang
Pei-Guang
PG
Sun
Liang-dan
LD
Zhang
Kai-Yue
KY
Wang
Beilan
B
Wang
Da-Zhi
DZ
Xu
Shi-Jie
SJ
Huang
Wei
W
Liu
Jian-Jun
JJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism
D019409:Interleukin-15