Human leukocyte antigen alleles and susceptibility to psoriatic arthritis |
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Authors: | Vinod Chandran Shelley B. Bull Fawnda J. Pellett Renise Ayearst Proton Rahman Dafna D. Gladman |
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Affiliation: | 1. Psoriatic Arthritis Program, Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada;2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada;3. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;4. Memorial University of Newfoundland, St. John’s, Newfoundland, Canada |
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Abstract: | ObjectiveOur purpose was to determine associations between HLA alleles and psoriatic arthritis (PsA).Methods678 PsA cases and 688 healthy controls were analyzed in a case–control design. The difference in the proportion of cases and controls with at least 1 copy of HLA alleles were tested for significance using χ2 test and Fisher’s exact test. Association analyses of haplotypes inferred by the Expectation–Maximization algorithm were performed. In the family-based association study, data from 283 families were analyzed.ResultsUnivariate analysis revealed that cases were more likely to be carriers of HLA-C∗01, -C∗02, -C∗06, -C∗12, -B∗27, -B∗38 and -B∗57, whereas controls were more likely to be carriers of HLA-C∗03, -C∗07, -B∗07, -B∗51, -DRB1∗15 and -DQB1∗0602. In haplotype analyses, PsA cases were more likely to be carriers of the HLA haplotypes -C∗01/-B∗27, -C∗02/-B∗27, -C∗12/-B∗38, and -C∗06/-B∗57, while controls were more likely to be carriers of the haplotypes -C∗07/-B∗07 and -C∗15/-B∗51. In the family-based association analysis, the HLA alleles -A∗02, -B∗27 and -DRB1∗07 were preferentially transmitted to cases, whereas the alleles -A∗03, -A∗28, -B∗51, -DRB1∗11 and -DQB1∗0301 were under transmitted.ConclusionThis large case–control and family based association study shows that HLA-C∗12/B∗38, HLA-B∗27 and HLA-C∗06/B∗57 are haplotypes (alleles) robustly associated with PsA. However, since patients with PsA also have psoriasis it is difficult to determine whether the primary association is with arthritis or psoriasis. |
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Keywords: | AS, ankylosing spondylitis CASP, Collaborative Association Study of Psoriasis CASPAR, classification criteria for psoriatic arthritis CD, cluster of differentiation DNA, deoxyribonucleic acid EM, Expectation&ndash Maximization FBAT, family-based association test FDR, false discovery rate GWAS, genome-wide association study HLA, human leukocyte antigen JIA, juvenile idiopathic arthritis KIR, killer-cell immunoglobulin-like receptors LD, linkage disequilibrium MHC, major histocompatibility complex NK, natural killer OR, odds ratio PCA, principal component analysis PCR, polymerase chain reaction PsA, psoriatic arthritis SNP, single nucleotide polymorphisms SpA, spondyloarthritis SSO, sequence specific oligonucleotide SSP, sequence specific primers WHO, World Health Organization |
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