Common variants of ZNF750, RPTOR and TRAF3IP2 genes and psoriasis risk

T Dębniak,Z Adamski,P Serrano-Fernandez,M Boer,A Mirecka,L Krysztoforska,E Soczawa,R Maleszka,J Lubinski,J Wiśniewska,K Paszkowska-Szczur,M Różewicka-Czabańska

doi:10.1007/s00403-013-1407-9

Abstract

Psoriasis vulgaris is a genetically heterogenous disease with unclear molecular background. We assessed the association of psoriasis and its main clinical phenotypes with common variants of three potential psoriasis susceptibility genes: ZNF750, RPTOR and TRAF31P2. We genotyped 10 common variants in a cohort of 1,034 case–control individuals using Taqman genotyping assays and sequencing. Minor alleles of all four TRAF3IP2 variants were more frequent among cases. The strongest, significant association was observed for rs33980500 (OR = 2.5, p = 0.01790). Minor allele of this SNP was always present in two haplotypes found to be associated with increased psoriasis risk: rs13196377_G + rs13190932_G + rs33980500_T + rs13210247_A (OR = 2.7, p = 0.0054) and rs13196377_A + rs13190932_A + rs33980500_T + rs13210247_G (OR = 1.8, p = 0.0008). Analyses of clinically relevant phenotypes revealed association of rs33980500 with pustular psoriasis (OR = 1.2, p = 0.0109). We observed significant connection of severity of cutaneous disease with variation at rs13190932 and suggestive with three remaining TRAF3IP2 SNPs. Another positive associations were found between age of onset and familial aggregation of disease: smoking and younger age of onset, smoking and occurrence of pustular psoriasis, nail involvement and arthropatic psoriasis, nail involvement and more severe course of psoriasis. We found no statistically significant differences in the prevalence of the examined variants of RPTOR and ZNF750 genes among our cases and controls. We have replicated the association of TRAF3IP2-_rs33980500 variant with the susceptibility to psoriasis. We have found new associations with clinically relevant subphenotypes such as pustular psoriasis or moderate-to-severe cases. We ascertain no connection of RPTOR and ZNF750 variants with psoriasis or its subphenotypes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00403-013-1407-9) contains supplementary material, which is available to authorized users.

Highlights

Psoriasis is one of the most common skin disorders
We assessed the association of psoriasis and its main clinical phenotypes with common variants of three potential psoriasis susceptibility genes: zincfinger 750 (ZNF750), RPTOR and TRAF31P2
Current evidence suggests that psoriasis is an immune-mediated disorder and novel therapies involved in the suppression of the immune responses, such as the T cell-targeted agents and tumor necrosis factor (TNF) inhibitors, have improved the outcome of the disease [9, 18]

Summary

Introduction

Psoriasis is one of the most common skin disorders. It is estimated that it affects 2–3 % of general CaucasianArch Dermatol Res (2014) 306:231–238 population [19]. Three GWAS studies identified 6q21 as a new psoriasis susceptibility locus and suggested a possible association of TRAF31P2 gene (OMIM 607043) with this disease [7, 8, 13]. Recent studies indicate that mutations/polymorphisms within CARD14 gene, located within this locus, predispose to psoriasis [15, 16]. Due to paucity and partial divergence of the ZNF750 and RPTOR literature data, it is justified to perform populationbased association study to evaluate possible link between selected mutations/polymorphisms of these genes and psoriasis. We genotyped ten common variants of ZNF750, Rptor and TRAF31P2 genes in our case–control cohort (n = 1034) from Polish population and evaluated main clinical phenotypes of psoriasis.

Methods

Results

Conclusion