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Association analysis of the skin barrier gene cystatin A at the PSORS5 locus in psoriatic patients: evidence for interaction between PSORS1 and PSORS5'

Vasilopoulos, Y., Walters, K., Cork, M.J., Duff, D.W., Sagoo, G.S. and Tazi-Ahnini, R. (2008) Association analysis of the skin barrier gene cystatin A at the PSORS5 locus in psoriatic patients: evidence for interaction between PSORS1 and PSORS5'. European Journal of Human Genetics, 16 (8). pp. 1002-1009. ISSN 1018-4813

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Abstract

Family-based analysis has revealed several loci for psoriasis and the locus, PSORS5, on chromosome 3q21 has been found in two independent studies. In this region, cystatin A (CSTA) encodes a skin barrier cystein protease inhibitor found in human sweat and it is over-expressed in psoriatic skin. Three CSTA markers at positions –190 (g.−190T>C), +162 (c.162T>C) and +344 (c.344C>T) were analysed in 107 unrelated patients and 216 matched controls. There was a significant trend for association with CSTA c.162T>C and psoriasis (odds ratio (OR)=3.45, P<0.001). Analysis of constructed haplotypes showed a highly significant association between disease and CSTA –190T/+162C/+344C (CSTA TCC) (P=10−6). In independent study, a TDT analysis in 126 nuclear families confirmed the over-transmission of CSTA TCC (P=0.0001). The presence of statistical interaction between CSTA TCC haplotype and HLA-Cw6 at PSORS1 locus was detected by performing TDT analysis on CSTA haplotypes stratified by the presence or absence of the risk allele at HLA-Cw6 locus. To estimate the disease risk we employed conditional logistic regression on the family data. The CSTA TCC haplotype is only associated with psoriasis in those individuals carrying the risk allele at the HLA-Cw6 locus (OR=2.22, P=0.0004, 95% CI= 1.42, 3.49). These results represent a major step towards the dissection of genetic factors involved in the pathogenesis of psoriasis.

Item Type: Article
Keywords: Skin barrier; cystatin; PSORS1; psoriasis
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield)
Depositing User: Mrs Megan Hobbs
Date Deposited: 22 Mar 2010 10:25
Last Modified: 07 Jun 2010 11:10
Published Version: http://dx.doi.org/10.1038/ejhg.2008.40
Status: Published
Publisher: Nature Publishing Group
Identification Number: 10.1038/ejhg.2008.40
URI: http://eprints.whiterose.ac.uk/id/eprint/10631

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