. (2011) Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis. Osteoarthritis and Cartilage, Vol.19 (No.3). pp. 265-271. ISSN 1063-4584

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Abstract

Objective: To clarify the role of common genetic variation in the Interleukin-1 beta (IL1B) and Interleukin-1R antagonist (IL1RN) genes on risk of knee and hip osteoarthritis (OA) and severity of knee OA by means of large-scale meta-analyses. Methods: We searched PubMed for articles assessing the role of IL1B and IL1RN polymorphisms/haplotypes on the risk of hip and/or knee OA. Novel data were included from eight unpublished studies. Meta-analyses were performed using fixed- and random-effects models with a total of 3595 hip OA and 5013 knee OA cases, and 6559 and 9132 controls respectively. The role of ILRN haplotypes on radiographic severity of knee OA was tested in 1918 cases with Kellgren-Lawrence (K/L) 1 or 2 compared to 199 cases with K/L 3 or 4. Results: The meta-analysis of six published studies retrieved from the literature search and eight unpublished studies showed no evidence of association between common genetic variation in the IL1B or IL1RN genes and risk of hip OA or knee OA (P > 0.05 for rs16944, rs1143634, rs419598 and haplotype C-G-C (rs1143634, rs16944 and rs419598) previously implicated in risk of hip OA). The C-T-A haplotype formed by rs419598, rs315952 and rs9005, previously implicated in radiographic severity of knee OA, was associated with reduced severity of knee OA (odds ratio (OR) = 0.71 95% CI 0.56-0.91; P = 0.006, I(2) = 74%), and achieved borderline statistical significance in a random-effects model (OR = 0.61 95% CI 0.35-1.06 P=0.08). Conclusion: Common genetic variation in the Interleukin-1 region is not associated with prevalence of hip or knee OA but our data suggest that IL1RN might have a role in severity of knee OA. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Osteoarthritis and Cartilage
Publisher:	Elsevier Science BV
ISSN:	1063-4584
Date:	March 2011
Volume:	Vol.19
Number:	No.3
Page Range:	pp. 265-271
Identification Number:	10.1016/j.joca.2010.12.003
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	European Commission (EC), Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO), Arthritis Research Campaign (UK) , Medical Research Council (UK) (MRC), Oxford NIHR Musculoskeletal Biomedical Research Unit , Estonian Science Foundation , Estonian Ministry of Social Affairs , Interleukin Genetics , National Institutes of Health (NIH), Wellcome Trust (UK) , AstraZeneca, Macclesfield UK , Arthritis Research Campaign , Leiden University Medical Centre , Dutch Arthritis Association , Pfizer Inc., Groton, CT, USA , Netherlands Organisation for Scientific Research (NWO), Centre of Medical System Biology , Netherlands Consortium for Healthy Aging
Grant number:	200800 (EC), 050-060-810 (NGI/NWO), 5308 (Estonian Science Foundation), 9.6-4/2035 12.1-5/597 (Estonian Ministry of Social Affairs), RO1 AR052873 (NIH), 14851 (Arthritis Research Campaign), MW 904-61-095 911-03-016 917 66344 911-03-012 (NWO)
URI:	http://wrap.warwick.ac.uk/id/eprint/41725

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