Objectives: 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).
Conclusion: This study confirms the association of the KIR2DS gene, especially KIR2DS2, with PsA.
Keywords: NK cell; genetic association; innate immunity; interaction; psoriasis.