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Human leukocyte antigen alleles and susceptibility to psoriatic arthritis
Authors:Vinod Chandran  Shelley B. Bull  Fawnda J. Pellett  Renise Ayearst  Proton Rahman  Dafna D. Gladman
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
Abstract:

Objective

Our purpose was to determine associations between HLA alleles and psoriatic arthritis (PsA).

Methods

678 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.

Results

Univariate analysis revealed that cases were more likely to be carriers of HLA-C01, -C02, -C06, -C12, -B27, -B38 and -B57, whereas controls were more likely to be carriers of HLA-C03, -C07, -B07, -B51, -DRB115 and -DQB10602. In haplotype analyses, PsA cases were more likely to be carriers of the HLA haplotypes -C01/-B27, -C02/-B27, -C12/-B38, and -C06/-B57, while controls were more likely to be carriers of the haplotypes -C07/-B07 and -C15/-B51. In the family-based association analysis, the HLA alleles -A02, -B27 and -DRB107 were preferentially transmitted to cases, whereas the alleles -A03, -A28, -B51, -DRB111 and -DQB10301 were under transmitted.

Conclusion

This large case–control and family based association study shows that HLA-C12/B38, HLA-B27 and HLA-C06/B57 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.
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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