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Association of Interleukin 23 Receptor Variants with Psoriatic Arthritis

PROTON RAHMAN, ROBERT D. INMAN, WALTER P. MAKSYMOWYCH, JEFF P. REEVE, LYNETTE PEDDLE, and DAFNA D. GLADMAN

ABSTRACT.

Objective. A recent genome-wide pooling study noted a significant association of interleukin 23 receptor (IL-23R) and psoriasis. Overxpression of IL-23 has been detected in lesional psoriatic skin, and induces epidermal proliferation. Given the interplay between psoriasis and PsA, we examined the association of IL-23R variants in 2 independent Canadian Caucasian cohorts of patients with psoriatic arthritis (PsA).

Methods. We examined 496 PsA probands and 476 controls. Cases and controls were genotyped for a panel of 11 single-nucleotide polymorphisms (SNP) in IL-23R. Allele and haplotype associations were calculated using WHAP software. P values for haplotype associations were calculated using a permutation test.

Results. The 381Gln allele of the coding SNP Arg381Gln (rs11209026) was found to be protective in the Canadian population (p = 0.004; corrected p = 0.044). A 2-marker haplotype from SNP rs7530511 and rs11209026 was associated with PsA (p = 0.011). All 3-marker sliding windows containing SNP rs11209026 were associated with PsA (p = 0.02 for all 3 windows). The magnitude of effect of IL-23R association in PsA appears to be similar to that reported in uncomplicated psoriasis.

Conclusion. Significant associations between Arg381Gln SNP and haplotypes encoding this variant were noted in PsA. It remains to be determined what contribution of this association, if any, is specifically due to the inflammatory arthritis (PsA) rather than psoriasis. (First Release Dec 1 2008; doi:10.3899/jrheum.080458)

Key Indexing Terms:

PSORIATIC ARTHRITIS
PSORIASIS
INTERLEUKIN 23R
GENETIC ASSOCIATION
Arg381Gln
SINGLE-NUCLEOTIDE POLYMORPHISM

From the Department of Medicine, Memorial University, St. John's, Newfoundland; Departments of Medicine and Immunology, University of Toronto, Toronto, Ontario; and Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

P. Rahman, MD, FRCPC, Professor, Department of Medicine, Memorial University; R.D. Inman, MD, FRCPC, Professor, Departments of Medicine and Immunology, University of Toronto; W.P. Maksymowych, MD, FRCPC, Professor; J.P. Reeve, PhD, Research Associate, Department of Medicine, University of Alberta; L. Peddle, BSc, Research Technician, Memorial University; D.D. Gladman MD, FRCPC, Professor, Department of Medicine, University of Toronto.

Address reprint requests to Dr. P. Rahman, Memorial University, 154 Le Marchant Road, St. John's, NL A1C 5B8. E-mail: prahman@mun.ca

Accepted for publication August 18, 2008.