title: Killer-cell immunoglobulin-like receptor gene polymorphisms and susceptibility to psoriatic arthritis.
abstract: OBJECTIVE
  We conducted a case-control study to determine the association between KIR2D and KIR3D gene polymorphisms and their interaction with HLA alleles in PsA.
  
  
  METHODS
  A total of 678 subjects with PsA and 688 healthy controls were studied. Differences between cases and controls in the frequency of individual KIR polymorphisms were tested for significance by an asymptotic χ(2) test and Fisher's exact test. Trends for increasing susceptibility to PsA from combined genotypes (HLA-KIR and HLA) were evaluated by the Cochran-Armitage trend test. Multigene logistic regression analysis was conducted to identify independent associations and interactions.
  
  
  RESULTS
  In univariate analyses, KIR2DL2 and KIR2DS2 polymorphisms were significantly associated with PsA. Only KIR2DS2 was associated with PsA compared with healthy controls in multivariate analysis [odds ratio (OR) 1.25, 95% CI 1.01, 1.54, P = 0.044]. The presence of HLA-C group 2 alleles was associated with a higher risk of PsA (trend test P = 0.006). The risk of PsA is higher when KIR2DS2 is present with the HLA-C ligands (C group 1) for the corresponding inhibitory KIRs, and is highest when KIR2DS2 is present in the absence of HLA-C ligands for homologous inhibitor KIRs, compared with the state when KIR2DS2 is absent (trend test P = 0.027). The presence of HLA-C alleles that have high cell surface expression was also associated with a higher risk of PsA (trend test P < 0.001). HLA-B Bw4 and HLA-B Bw4 80ile allele groups were associated with a higher PsA risk (trend test P < 0.0001 for both analyses).
  
  
  CONCLUSIONS
  This study confirms the association of the KIR2DS gene, especially KIR2DS2, with PsA.
authors.affiliation: Psoriatic Arthritis Program, Toronto Western Research Institute, Toronto Western Hospital, Centre for Prognosis Studies in the Rheumatic Diseases, University of Toronto, 399 Bathurst Street, Room 1E-410, Toronto, ON, Canada M5T 2S8. dafna.gladman@utoronto.ca.
authors.forename: Vinod
authors.initials: V
authors.lastname: Chandran
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Bull
authors.forename: Fawnda J
authors.initials: FJ
authors.lastname: Pellett
authors.forename: Renise
authors.initials: R
authors.lastname: Ayearst
authors.forename: Remy A
authors.initials: RA
authors.lastname: Pollock
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
mesh_terms: D000328:Adult; D000483:Alleles; D015535:Arthritis, Psoriatic / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000235:genetics*; D054343:Receptors, KIR2DL2 / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; C433932:KIR2DS2 protein, human; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2
keywords: NK cell; genetic association; innate immunity; interaction; psoriasis