Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Association between Killer-Cell Immunoglobulin-Like Receptor (KIR) Gene Polymorphisms and Psoriatic Arthritis (PsA).

Chandran2,  Vinod, Pellett2,  Fawnda, Ayearst2,  Renise, Pollock2,  Remy, Gladman1,  Dafna D.

Toronto Western Hospital, Toronto, ON, Canada
University of Toronto Psoriatic Arthritis Clinic, Toronto Western Hospital

Background:

KIR genes within the leukocyte receptor complex on chromosome 19q are associated with PsA. We sought to further characterize this association and determine whether the associations are independent of HLA allele associations.

Methods:

685 cases of European ethnicity (295 females, mean age 43 years, PsA duration 7 years, psoriasis duration 15 years, actively inflamed joint count 11, PASI score 5.2) with PsA and 706 ethnically matched controls (273 females, mean age 53 years) were recruited for the study. Genotyping for 15 KIR genes was performed on genomic DNA obtained from peripheral blood using PCR-SSP and that for HLA-B, and -C alleles was performed using PCR-SSO reverse line blot. Phenotype frequencies (frequencies of individuals positive for each gene or allele) were calculated and differences between cases and controls determined using Fisher's exact test using a dominant model. Multivariate logistic regressions were performed, including all KIR genes present in <95% of cases or controls, and HLA alleles present in >5% of cases and controls and significant in univariate analyses. Association of KIR2DS1 and KIR2DS2 with PsA in the presence/absence of HLA-Cgrp2 (HLA-C*02, C*04, C*05, C*06) and Cgrp1 (HLA-C*01, C*03, C*07, C*08) ligands for their corresponding inhibitory KIRs (KIR2DL1 and KIR2DL2/2DL3 respectively) was also investigated using chi- square test and evidence of trend with combined risk genotypes determined using Mantel-Haenszel trend test.

Results:

In univariate analyses, KIR2DS2 (Odds ratio 1.13 p = 0.028), KIR2DL2 (OR 1.13, p = 0.031), HLA-B*07 (OR 0.56, p<0.0001), B*13 (OR 1.73, p = 0.016), B*27 (OR 3.04, p <0.0001), B38 (OR 7.24, p <0.0001), B39 (OR 2.04, p = 0.008), B51 (OR 0.45, p <0.0001), B*57 (OR 1.81, p <0.0001), B*60 (OR 0.58, p =0.008), C*01 (OR 1.89, p =0.002), C*02 (OR 1.98, p <0.0001), C*03 (OR 0.64, p =0.002), C*04 (OR 0.74, p =0.027), C*06 (OR 1.65, p <0.0001), C*07 (OR 0.66, p<0.0001), C*12 (OR 2.38, p <0.0001) and C*15 (OR 0.48, P=0.005) were significantly associated with PsA. The results of the multivariate analysis using logistic regression with backward selection are given in Table 1.

Table 1. Results of multivariate logistic regression analyses using HLA alleles found significant in the univariate analyses as well as KIR genes present in <95% of the population as explanatory variables.

Allele/GenotypeOdds Ratio95% Confidence IntervalP value
HLA-B*070.710.54, 0.940.0169
HLA-B*132.141.35, 3.40.0012
HLA-B*273.522.46, 5.03<0.0001
HLA-B*388.224.66, 14.51<0.0001
HLA-B*392.541.49, 4.340.0006
HLA-B*510.530.34, 0.810.0038
HLA-B8572.301.61, 3.3<0.0001
HLA-C*030.740.56, 0.990.0457
KIR2DS21.311.04, 1.640.0205

HLA-B*13, B*27, B*38, B*39 and B*57 were found to increase PsA risk whereas HLA-B*07, B*51 and C*03 were protective. Among the KIR genes only KIR2DS2 was found to significantly increase risk for PsA after adjusting for HLA-B and -C associations. Association between PsA and combined KIR2DS2 and HLA-Cgrp1 risk genotypes was demonstrated (trend p= 0.024). Although, chi square test using combined KIR2DS1 and HLA-Cgrp2 genotypes showed evidence of association (p = 0.025), no evidence of a trend could be demonstrated (trend p = 0.81).

Conclusions:

KIR2DS2 is associated with PsA independent of HLA alleles. The risk for PsA increases with the presence of KIR2DS2 in the absence of ligands for KIR2DL2/2DL3 with risk being highest when KIR2DS2 is present in the absence of HLA-Cgrp1 alleles.

To cite this abstract, please use the following information:
Chandran, Vinod, Pellett, Fawnda, Ayearst, Renise, Pollock, Remy, Gladman, Dafna D.; Association between Killer-Cell Immunoglobulin-Like Receptor (KIR) Gene Polymorphisms and Psoriatic Arthritis (PsA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1966
DOI: 10.1002/art.29731

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