ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1901

Genetic Variants In OPG and ANKH Are Associated With Severity Ofankylosis In Ankylosing Spondylitis In a Korean Cohort

Il-Hoon Sung1, Tae-Hwan Kim2, Young Bin Joo3, So-Young Bang4, Seunghun Lee5, Kyung-Bin Joo6, Proton Rahman7, Darren D. O'Rielly7 and Robert Inman8, 1Orthopaedic surgery, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 2Division of Rheumatology, Department of Internal Medicine, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 3Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 4Hanyang University Guri Hospital, Guri, South Korea, 5Department of Radiology, Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 6Department of Radiology, Department of Radiology, Hanynag University Hospital for Rheumatic Diseases, Seoul, South Korea, 7Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada, 8Immunlogy and Institute of Medical Science, University of Toronto and Toronto Western Hospital, Toronto, ON, Canada

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Genetics and Genomics of Rheumatic Disease II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Spinal ankylosis,which represents the most severe radiologic change in ankylosing spondylitis (AS),is associated with permanent work disability as well as decreased quality of life. Clinically, male sex, younger age at symptom onset, smoking, and elevated C-reactive protein level have been identified as factors associated with radiologic severity. However, genetic factors associated with radiologic severity remains elusivealthough AS is thought to be largely genetically determined.Thus, weset out to investigate which polymorphismsamong genes involved in bone formationwas associated with radiologic severity.Particular emphasis was placed on genes involved inWNT/β-catenin pathway and their respectiveantagonists or agonists. We also set out to investigatepossible genetic-environmental interactions which could also impact AS radiologic severity.

Methods: A total of 417 Korean AS patients were enrolledand wereclassified into two groups based on the radiologic severity as defined bymSASSS: (1) Severe ankylosis (2) Control AS. Severe ankylosiswas defined in the cases which had two intervertebral adjacent bridges (mSASSS score 2 at each site) and/or fusion (mSASSS score 3 at each site) in the lumbar spine or cervical spine.Control AS was defined in the cases which had no or only 1syndesmophytes or bridging.There were 148patients in the first group and259 patients in the second. A total of 366 single nucleotide polymorphisms within 52 genes were genotyped using the SequenomMassARRAY® system (iPLEX GOLD). Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by logistic regression controlling for age and disease duration as covariates to identify the genetic predictors of radiologic severity.

Results: SNP rs1032128 (in OPG or TNFRSF11B) and rs2453327 (in ANKH) showed the most significant associations with severe ankylosis(P =6.49×10-4, OR = 0.56, 95%, and P =1.08×10-3, OR = 1.72, respectively) after adjusting age and disease duration.In multivariate analyses, smoking(OR = 1.87, 95% CI 1.19-2.95) was significantly associated with severity ofankylosis. The combination of smoking and SNP rs1032128 A increased the risk of ankylosis 4.56-fold (95% CI 2.104-9.889) comparing to that of nonsmoker and SNP rs1032128G,and the combination of smoking and SNP rs2453327Tincreased the risk of ankylosis 2.89-fold(95% CI 1.586-5.277) comparing to that of nonsmoker and SNP rs2453327C.

Conclusion: Genetic polymorphisms in the bone-related genes OPG and ANKHdemonstrate a significant association with severity of ankylosis in Korean AS, and theseassociationsareenhancedin smoker.

Disclosure:

I. H. Sung,
None;

T. H. Kim,
None;

Y. B. Joo,
None;

S. Y. Bang,
None;

S. Lee,
None;

K. B. Joo,
None;

P. Rahman,

Amgen, Abbott, BMS, Merck, Pfizer, Janssen, Hoffman-La Roche, UCB, Novartis, Sanofi-Aventis,

5,

Amgen, Abbott, BMS, Merck, Pfizer, Janssen, Hoffman-La Roche, UCB, Novartis, Sanofi-Aventis,

9;

D. D. O’Rielly,
None;

R. Inman,
None.

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