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... Show moreObjective: 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 Novel data were included from eight unpublished studies.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 Results: The meta-analysis of six published studies retrieved from the literature search and eight unpublished studies showed no evidence of association between common genetic variation in the IL1B or IL1RN genes and risk of hip OA or knee OA (P 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. Show less
Objective Several research groups have examined osteoarthritis (OA) association with Interleukin-1 (IL-1) region markers and haplotypes The results have been suggestive for hand OA, negative for... Show moreObjective Several research groups have examined osteoarthritis (OA) association with Interleukin-1 (IL-1) region markers and haplotypes The results have been suggestive for hand OA, negative for knee OA, and conflicting for hip OA Design Our aim was to address conflicts employing meta-analytical methods on data from 1238 European-descent cases with various OA phenotypes and 1269 European-descent controls from four study centers We imputed some missing genotype data and reconstructed IL-1 region extended haplotypes A previously reported 7-marker IL1A-IL1B-IL1RN extended risk haplotype was tested for association with each specific index phenotype Results. For hip OA, data from three centers showed heterogeneity of extended-risk-haplotype effect, two panels showing trend toward risk and another showing protection, with overall odds ratio (OR) 1 24 (95% Confidence interval (CI) 0 45-3 41, P 0 67) The heterogeneity fell partly along control ascertainment lines, chiefly between controls ascertained as spouses of arthroplasty patients and controls identified through population radiographic survey For knee OA, the results showed no heterogeneity and no significant extended-risk-haplotype effect For hand OA, the results showed little heterogeneity and a modest trend toward positive association (summary OR 1 34, 95% CI 0 83-2 17 P 023) Using a Bayesian partition modeling approach, the 7-marker extended haplotypes showed no significant effect on any OA phenotype examined A 3-single-nucleotide polymorphism (SNP) IL1B-IL1RN haplotype rs1143627-rs16944-rs419598 showed a trend toward hand OA association (posterior probability of association 0 72) with the most prominent feature being protection from a specific haplotype representing a partial mirror image of the extended risk haplotype (OR estimated at 0 46) Conclusions The meta-analysis data do not confirm but only suggest that some hand and hip OA risk could be associated with the IL-1 region, particularly centered in IL1B and possibly also IL1RN (C) 2009 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International Show less
