title: Common variants of ZNF750, RPTOR and TRAF3IP2 genes and psoriasis risk.
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.
authors.affiliation: Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Połabska 4, 70-115, Szczecin, Poland, debniak@pum.edu.pl.
authors.forename: T
authors.initials: T
authors.lastname: Dębniak
authors.forename: E
authors.initials: E
authors.lastname: Soczawa
authors.forename: M
authors.initials: M
authors.lastname: Boer
authors.forename: M
authors.initials: M
authors.lastname: Różewicka-Czabańska
authors.forename: J
authors.initials: J
authors.lastname: Wiśniewska
authors.forename: P
authors.initials: P
authors.lastname: Serrano-Fernandez
authors.forename: A
authors.initials: A
authors.lastname: Mirecka
authors.forename: K
authors.initials: K
authors.lastname: Paszkowska-Szczur
authors.forename: J
authors.initials: J
authors.lastname: Lubinski
authors.forename: L
authors.initials: L
authors.lastname: Krysztoforska
authors.forename: Z
authors.initials: Z
authors.lastname: Adamski
authors.forename: R
authors.initials: R
authors.lastname: Maleszka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011565:Psoriasis / Q000175:diagnosis / Q000235:genetics*; D000076223:Regulatory-Associated Protein of mTOR; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; C414202:TRAF3IP2 protein, human; D014157:Transcription Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D025521:Tumor Suppressor Proteins; C570799:ZNF750 protein, human