title: Evidence for susceptibility determinant(s) to psoriasis vulgaris in or near PTPN22 in German patients.
abstract: BACKGROUND
  Variant R620W of protein tyrosine phosphatase non-receptor type 22 (PTPN22) has consistently been reported as a susceptibility factor for several autoimmune diseases. We investigated its role in susceptibility to psoriasis, the relevance of possibly other disease-causing variants, and interdependency of the major risk factor for psoriasis at PSORS1.
  
  
  METHODS
  R620W was tested in a case-control study initially with 375 German patients and then with an enlarged sample of an additional 418 patients. Analyses were extended to linkage disequilibrium (LD) based haplotypes. Potential interaction between risk haplotypes of PTPN22 and the PSORS1 associated risk allele was tested by regression analysis. PTPN22 coding sequence was determined in 20 patients carrying the risk haplotype. Association and regression analysis were also performed in the extended case-control study.
  
  
  RESULTS
  R620W was not associated in either case-control study, while significant association (corrected for multiple testing) with one haplotype (C-4) of the LD block encompassing PTPN22 as well with another haplotype (B-3) within an adjacent telomeric LD block was detected. No evidence for interaction between risk haplotype C-4 and the PSORS1 associated risk allele was found. Sequencing excluded other coding variants within PTPN22 as a basis for association findings. Analysis of the extended study group confirmed association for haplotypes B-3 and C-4 and independence of risk haplotypes C-4 and PSORS1.
  
  
  CONCLUSIONS
  We exclude a major role of *620W in German psoriasis patients but suggest that other susceptibility determinant(s) within non-coding regions of PTPN22 or its proximity might exist acting independently of the major PSORS1 risk factor.
authors.affiliation: Institute of Human Genetics, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hüffmeier
authors.forename: M
authors.initials: M
authors.lastname: Steffens
authors.forename: H
authors.initials: H
authors.lastname: Burkhardt
authors.forename: J
authors.initials: J
authors.lastname: Lascorz
authors.forename: F
authors.initials: F
authors.lastname: Schürmeier-Horst
authors.forename: M
authors.initials: M
authors.lastname: Ständer
authors.forename: R
authors.initials: R
authors.lastname: Kelsch
authors.forename: C
authors.initials: C
authors.lastname: Baumann
authors.forename: W
authors.initials: W
authors.lastname: Küster
authors.forename: R
authors.initials: R
authors.lastname: Mössner
authors.forename: K
authors.initials: K
authors.lastname: Reich
authors.forename: T F
authors.initials: TF
authors.lastname: Wienker
authors.forename: H
authors.initials: H
authors.lastname: Traupe
authors.forename: A
authors.initials: A
authors.lastname: Reis
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011565:Psoriasis / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases