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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

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
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
Objective: To clarify the role of common genetic variation in the Interleukin-1? (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 Novel data were included from eight unpublished studies.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Results: The meta-analysis of six published studies retrieved from the literature search and eight unpublished studies showed no evidence of association between common genetic variation in the IL1B or IL1RN genes and risk of hip OA or knee OA (P 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, I2 = 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.
osteoarthritis, il-1, interleukin, genetic, association, polymorphism
1063-4584
265-271
Kerkhof, H.J.M.
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Doherty, M.
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Arden, N.K.
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Abramson, S.B.
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Attur, M.
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Bos, S.D.
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Cooper, C.
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Dennison, E.M.
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Doherty, S.A.
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Evangelou, E.
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Hart, D.J.
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Hofman, A.
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Javaid, K.
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Kerna, I.
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Kisand, K.
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Kloppenburg, M.
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Krasnokutsky, S.
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Maciewicz, R.A.
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Meulenbelt, I.
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Muir, K.R.
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Rivadeneira, F.
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Samuels, J.
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Sezgin, M.
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Slagboom, E.
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Smith, A.J.P.
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Spector, T.D.
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Tamm, A.
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Uitterlinden, A.G.
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Wheeler, M.
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Zhai, G.
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Zhang, W.
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van Meurs, J.B.J.
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Valdes, A.M.
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Kerkhof, H.J.M.
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Doherty, M.
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Arden, N.K.
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Abramson, S.B.
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Attur, M.
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Bos, S.D.
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Cooper, C.
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Dennison, E.M.
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Doherty, S.A.
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Evangelou, E.
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Hart, D.J.
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Hofman, A.
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Javaid, K.
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Kerna, I.
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Kisand, K.
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Kloppenburg, M.
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Krasnokutsky, S.
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Maciewicz, R.A.
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Meulenbelt, I.
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Muir, K.R.
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Rivadeneira, F.
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Samuels, J.
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Sezgin, M.
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Slagboom, E.
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Smith, A.J.P.
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Spector, T.D.
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Tamm, A.
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Uitterlinden, A.G.
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Wheeler, M.
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Zhai, G.
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Zhang, W.
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van Meurs, J.B.J.
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Valdes, A.M.
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Kerkhof, H.J.M., Doherty, M., Arden, N.K., Abramson, S.B., Attur, M., Bos, S.D., Cooper, C., Dennison, E.M., Doherty, S.A., Evangelou, E., Hart, D.J., Hofman, A., Javaid, K., Kerna, I., Kisand, K., Kloppenburg, M., Krasnokutsky, S., Maciewicz, R.A., Meulenbelt, I., Muir, K.R., Rivadeneira, F., Samuels, J., Sezgin, M., Slagboom, E., Smith, A.J.P., Spector, T.D., Tamm, A., Uitterlinden, A.G., Wheeler, M., Zhai, G., Zhang, W., van Meurs, J.B.J. and Valdes, A.M. (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, 19 (3), 265-271. (doi:10.1016/j.joca.2010.12.003). (PMID:21146623)

Record type: Article

Abstract

Objective: To clarify the role of common genetic variation in the Interleukin-1? (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, I2 = 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.

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More information

Published date: March 2011
Keywords: osteoarthritis, il-1, interleukin, genetic, association, polymorphism

Identifiers

Local EPrints ID: 176121
URI: http://eprints.soton.ac.uk/id/eprint/176121
ISSN: 1063-4584
PURE UUID: cc820724-16f5-4225-b73a-4400c89c33a0
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for E.M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961

Catalogue record

Date deposited: 14 Mar 2011 14:30
Last modified: 18 Mar 2024 02:45

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Contributors

Author: H.J.M. Kerkhof
Author: M. Doherty
Author: N.K. Arden
Author: S.B. Abramson
Author: M. Attur
Author: S.D. Bos
Author: C. Cooper ORCID iD
Author: E.M. Dennison ORCID iD
Author: S.A. Doherty
Author: E. Evangelou
Author: D.J. Hart
Author: A. Hofman
Author: K. Javaid
Author: I. Kerna
Author: K. Kisand
Author: M. Kloppenburg
Author: S. Krasnokutsky
Author: R.A. Maciewicz
Author: I. Meulenbelt
Author: K.R. Muir
Author: F. Rivadeneira
Author: J. Samuels
Author: M. Sezgin
Author: E. Slagboom
Author: A.J.P. Smith
Author: T.D. Spector
Author: A. Tamm
Author: A.G. Uitterlinden
Author: M. Wheeler
Author: G. Zhai
Author: W. Zhang
Author: J.B.J. van Meurs
Author: A.M. Valdes

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