Association of interleukin-23 receptor variants with ankylosing spondylitis.
OBJECTIVE
Recent studies have shown that a nonsynonymous single-nucleotide polymorphism (SNP) (Arg381Gln; rs11209026) in the interleukin-23 receptor (IL-23R) gene on chromosome 1p31 is associated with Crohn's disease and psoriasis. Given the clinical and immunologic overlap between ankylosing spondylitis (AS) and these diseases, and the potential function of this candidate SNP, this study was undertaken to examine the association of IL-23R variants with AS in multiple Canadian populations.


METHODS
We examined 3 cohorts of AS patients from established rheumatic disease centers in Canada. The majority of AS patients were Caucasians of northern European descent, and all patients satisfied the modified New York classification criteria for AS or for juvenile spondylarthritis. We examined 424 AS probands and 401 controls from Alberta, 251 AS probands and 122 controls from Toronto, and 121 AS probands and 219 controls from Newfoundland. Ten IL-23R SNPs were genotyped, 9 of which were incorporated in the haplotype analysis. Allele and haplotype associations were calculated using the WHAP software package. P values for haplotype associations were calculated using a permutation test.


RESULTS
The primary SNP of interest in a previous study of inflammatory bowel disease (IBD) (Arg381Gln; rs11209026) was found to be protective against AS in the Newfoundland population (P=0.04) and in the Toronto population (P=0.04) in single-marker univariate analysis. The strongest association, however, was with SNP rs11465804 (P=0.007 for the Newfoundland population and P=0.0007 for the Toronto population). A 3-marker sliding window omnibus test revealed a significant association with markers rs10489629, rs2201841, and rs11465804 in both the Newfoundland population (P=0.04) and the Alberta population (P=0.034). Our results were independent of the IBD and psoriasis status of the AS patients.


CONCLUSIONS
This concurrent analysis of 3 distinct AS populations and their regional controls demonstrates a disease association with the IL-23R locus and implicates the same polymorphisms associated with IBD and psoriasis.
Rahman
Proton
P
Memorial University, St. John's, Newfoundland, Canada. prahman@mun.ca
Inman
Robert D
RD
Gladman
Dafna D
DD
Reeve
Jeff P
JP
Peddle
Lynette
L
Maksymowych
Walter P
WP
D000328:Adult; D002170:Canada; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics*
D018123:Receptors, Interleukin; C415369:interleukin-22 receptor