Human leucocyte antigen risk alleles for psoriatic arthritis among patients with psoriasis
- Lihi Eder1,
- Vinod Chandran1,
- Fawnda Pellet1,
- Sutha Shanmugarajah1,
- Cheryl F Rosen2,
- Shelley B Bull3,
- Dafna D Gladman1
- 1Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Canada
- 2Division of Dermatology, Toronto Western Hospital, University of Toronto, Toronto, Canada
- 3Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
- Correspondence to Dr Dafna D Gladman, University of Toronto Psoriatic Arthritis Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, 399 Bathurst Street, 1E-410B, Toronto M5T 2S8, Canada;
Contributors LE designed the study, collected data, wrote the statistical analysis plan, cleaned and analysed the data and wrote the manuscript. She is the guarantor. VC designed the study, collected data, analysed the data and revised the manuscript. FP designed the study, collected data, performed HLA genotyping and revised the manuscript. SS monitored data collection and data entry. CFR designed the study, monitored data collection and revised the paper. SBB assisted in the statistical analysis plan, analysed the data and revised the manuscript. DDG designed the study, monitored data collection for the whole trial, assisted in the statistical analysis plan, analysed the data and revised the paper.
- Accepted 3 August 2011
- Published Online First 6 September 2011
Aim Genes that differentiate patients with psoriatic arthritis (PsA) from those with cutaneous psoriasis (PsC) may serve as markers for the development of PsA in patients with psoriasis. The authors aimed to identify human leucocyte antigen (HLA) alleles that are associated with the development of PsA in patients with psoriasis.
Methods 712 adult patients with PsA, 335 adult patients with PsC and 713 healthy controls were genotyped for HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ alleles. Differences in allelic distributions for each of the HLA loci were compared using a likelihood ratio test. Logistic regression analysis of multiple loci was performed to account for linkage disequilibrium. Haplotype information was inferred using the expectation–maximisation algorithm (given HLA-C and HLA-B genotypes) and analysed similarly.
Results The following HLA alleles were found to be significantly associated with patients with PsA compared to patients with PsC in multivariate regression analysis: B*08 (OR 1.61, p=0.009), B*27 (OR 5.17, p<0.0001), B*38 (OR 1.65, p=0.026) and C*06 (OR 0.58, p=0.0002). HLA-B*27, HLA-B*38 and HLA-C*06 frequencies were also significantly higher in patients with PsA than in healthy controls (B*27: OR 3.05, p<0.0001; B*38: OR 5.9, p<0.0001; HLA-C*06: OR 1.71, p<0.0001). The following haplotypes were independently associated with PsA compared to PsC: HLA-B*18-C*07 (OR 10.1, p=0.004), HLA-B*27-C*01 (OR 41.1, p<0.0001), HLA-B*27-C*02 (OR 19.9, p<0.0001), HLA-B*38-C*12 (OR 2.9, p=0.01), HLA-B*08-C*07 (OR 2.6, p=0.004) and HLA-B*57-C*06 (OR 0.5, p=0.03).
Conclusions Certain HLA-B and HLA-C alleles confer susceptibility to PsA among patients with psoriasis and may be used to identify patients with PsC who may develop PsA.
Funding The University of Toronto PsA program was supported by a grant from the Krembil Foundation, as well as by The Arthritis Society SPARCC National Research Initiative. Dr Eder was supported by a fellowship grant from the Canadian Arthritis Network and by an Abbott PsA Fellowship. Dr Chandran was supported by a Canadian Institutes of Health Research—Clinical Research Initiative Fellowship and the Krembil Foundation.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the University Health Network.
Provenance and peer review Not commissioned; externally peer reviewed.