Radiographic severity of ankylosing spondylitis is associated with polymorphism of the large multifunctional peptidase 2 gene in the Spondyloarthritis Research Consortium of Canada cohort.
OBJECTIVE
There are limited data on genetic predictors of radiographic progression. The aim of this study was to examine polymorphisms in genes involved in antigen presentation and their effect on radiographic severity and progression.


METHODS
Caucasian patients with ankylosing spondylitis (AS) (diagnosed according to the modified New York criteria) from 2 Canadian centers were enrolled. Patients in the progression part of the study had at least 2 sets of radiographs obtained at a minimum gap of 1.5 years, with a modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Peripheral blood DNA was used for genotyping a panel of 13 coding-region single-nucleotide polymorphisms (SNPs) in ERAP1, LMP2, LMP7, TAP1, and TAP2. Linear regression analysis was performed to identify the predictors of the baseline mSASSS and logistic regression for predictors of progression. Progression was defined as an increase of 1 mSASSS unit per year.


RESULTS
A total of 241 AS patients (81% males; 82% HLA-B27-positive) were enrolled from the 2 centers for analysis of the predictors of baseline radiographic severity. In univariate analyses, the baseline mSASSS was associated with sex, disease duration, and SNPs rs30187 (ERAP1) and rs17587 (LMP2). In multivariate analyses, duration of disease (B = 0.74; P = 1 × 10(-11) ), sex (B = 12.1; P = 5 × 10(-5) ), and the LMP2 SNP rs17587 (B = 6.2; P = 0.01) were significantly associated with the baseline mSASSS. In multivariate analyses of progression, only the baseline mSASSS was a significant predictor (B = 0.03; P = 0.003).


CONCLUSIONS
This is the first study to demonstrate that LMP2 variants can affect radiographic severity in AS. The baseline mSASSS remains the strongest predictor of radiographic progression but explains only a fraction of the variability seen.
Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada.
Nigil
N
Haroon
Walter P
WP
Maksymowych
Proton
P
Rahman
Florence W L
FW
Tsui
Finbar D
FD
O'Shea
Robert D
RD
Inman
D000328:Adult; D000368:Aged; D002170:Canada; D015331:Cohort Studies; D003546:Cysteine Endopeptidases / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D012720:Severity of Illness Index; D013131:Spine / Q000000981:diagnostic imaging*; D013167:Spondylitis, Ankylosing / Q000000981:diagnostic imaging* / Q000235:genetics*
C071313:LMP-2 protein; D003546:Cysteine Endopeptidases