ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 979

HLA Class I Genes As Susceptibility Markers of Psoriatic Arthritis in Patients with Psoriasis – a Meta-Analysis

Lihi Eder1, Fatima Abji2, Cheryl Rosen3, Muhammad Haroon4, Vinod Chandran1, Rubén Queiro5, Shelley Bull6, Richard J. Cook7, Proton Rahman8, Robert Winchester9, Oliver FitzGerald10 and Dafna D. Gladman1, 1Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 2University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 3Dermatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, 4Kerry General Hospital, Tralee, Ireland, 5Rheumatology Service, Hospital Universitario Central de Asturias, Oviedo, Spain, 6School of Public Health, Mount Sinai Hospital, Toronto, ON, Canada, 7Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada, 8Computer Sciences, Memorial University of Newfoundland, St. John's, NF, Canada, 9Columbia University, New York, NY, 10Department of Rheumatology, St Vincent's University Hospital, Dublin, Ireland

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Sunday, November 8, 2015

Title: Spondylarthropathies Psoriatic Arthritis - Pathogenesis, Etiology

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

Genes that differentiate patients with psoriatic arthritis (PsA) from those with psoriasis alone may serve as markers for the development of PsA in psoriasis patients. Psoriatic disease risk is strongly associated with variation within the HLA class I region. In this large-scale study we aimed to strengthen evidence about previously reported HLA risk alleles for PsA and to identify novel susceptibility markers to the disease.

Methods:

1677 PsA, 702 psoriasis without arthritis and 2275 healthy controls of European ethnicity from 4 sites in Canada, Ireland and Spain were included in the study. HLA-B and –C alleles were genotyped using sequence specific primers. Differences in allelic distribution for each HLA locus were compared using the Likelihood Ratio test by regression models with site indicator. The False Discovery Rate (FDR) approach was employed to assess the impact of multiple testing. Logistic regression analysis was performed to account for linkage disequilibrium between HLA-B and -C alleles. The association between amino acids encoded by the identified HLAgenes and PsA was assessed using logistic regression analysis.

Results:

The following HLA alleles were confirmed as independent susceptibility markers of PsA in psoriasis patients in the multivariate analysis: B*08 (Odds Ratio (OR) 1.48, p=0.002), B*27 (OR 3.69, p=2.8×10-12), B*38 (OR 1.68, p=0.005), B*39 (OR 1.80, p=0.01) and C*06 (OR 0.47, p=6.8×10-13). The following HLA alleles were confirmed as susceptibility markers for PsA in the general population: B*27 (OR 2.37, p=2.5×10-13), B*38 (OR 3.81, p=2.5×10-13), B*39 (OR 2.17, p=9.5×10-6), B*57 (OR 2.06, p=3.6×10-7) and C*06 (OR 1.29, p=0.02). The frequency of the following alleles was reduced in PsA compared to healthy controls: B*07, B*44, B*40, B*15, B*49, B*51, B*55, C*04 and C*08. PsA susceptibility was also associated with the presence of cysteine at position 67 (B*27, B*39, B*38), methionine at position 67 (B*57), aspartate at position 9 (B*08) and glutamine at position 45 (B*08, B*39, B*38, B*27). However, after inclusion of the specific HLA risk alleles these associations were not statistically significant.

Conclusion:

PsA susceptibility is associated with several HLA class I alleles. HLA-B*38, B*39, B*08 and B*27 confer an increased risk for PsA compared to psoriasis. In contrast, HLA-C*06, the strongest psoriasis susceptibility gene, is associated with a lower risk of developing PsA in patients with psoriasis.

Disclosure: L. Eder, None; F. Abji, None; C. Rosen, None; M. Haroon, None; V. Chandran, None; R. Queiro, None; S. Bull, None; R. J. Cook, None; P. Rahman, None; R. Winchester, None; O. FitzGerald, None; D. D. Gladman, None.

To cite this abstract in AMA style:

Eder L, Abji F, Rosen C, Haroon M, Chandran V, Queiro R, Bull S, Cook RJ, Rahman P, Winchester R, FitzGerald O, Gladman DD. HLA Class I Genes As Susceptibility Markers of Psoriatic Arthritis in Patients with Psoriasis – a Meta-Analysis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/hla-class-i-genes-as-susceptibility-markers-of-psoriatic-arthritis-in-patients-with-psoriasis-a-meta-analysis/. Accessed .

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