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Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis

Muthuri, Stella G.; Doherty, Sally; Zhang, Weiya; Maciewicz, Rose A.; Muir, Kenneth R.; Doherty, Michael

Authors

Stella G. Muthuri

Sally Doherty

Weiya Zhang

Rose A. Maciewicz

Kenneth R. Muir

Michael Doherty



Abstract

Introduction: The objective was to investigate potential gene-environment interaction between body mass index (BMI) and each of eight TGFβ1 polymorphisms in knee and hip osteoarthritis (OA).
Methods: We conducted a case-control study of Caucasian men and women aged 45 to 86 years from Nottingham, United Kingdom (Genetics of OA and Lifestyle (GOAL) study). Cases had clinically severe symptoms and radiographic knee or hip OA; controls had no symptoms and no radiographic knee/hip OA. We used logistic regression to investigate the association of TGFβ1 polymorphisms and OA when stratifying by BMI. Knee and hip OA were analyzed separately with adjustment for potential confounders. Additive and multiplicative interactions were examined.
Results: 2,048 cases (1,042 knee OA, 1,006 hip OA) and 967 controls were studied. For hip OA, the highest risk was in overweight (BMI ≥25 kg/m2) individuals with the variant allele of single-nucleotide polymorphism (SNP)
rs1800468 (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.55, 3.15). Evaluation of gene-environment interaction indicated significant synergetic interaction (relative excess risk due to interaction (RERI) = 0.93, synergy index (SI) = 4.33) with an attributable proportion due to interaction (AP) of 42% (AP = 0.42; 95% CI 0.16, 0.68). Multiplicative interaction was also significant (OR for interaction (ORINT) = 2.27, P = 0.015). For knee OA, the highest risk was in overweight individuals with homozygous genotype 11 of SNP rs2278422 (OR = 6.95, P < 0.001). In contrast, the variant allele indicated slightly lower risks (OR = 4.72, P < 0.001), a significant antagonistic interaction (RERI = -2.66, SI = 0.59), AP = -0.56 (95%CI -0.94, -0.17) and a significant multiplicative interaction (ORINT = 0.47, P = 0.013).
Conclusion: TGFβ1 gene polymorphisms interact with being overweight to influence the risk of large joint OA.

Journal Article Type Article
Publication Date Apr 18, 2013
Journal Arthritis Research and Therapy (Deleted)
Electronic ISSN 1478-6354
Publisher Humana Press
Peer Reviewed Peer Reviewed
Volume 15
Issue 2
Article Number R52
Institution Citation Muthuri, S. G., Doherty, S., Zhang, W., Maciewicz, R. A., Muir, K. R., & Doherty, M. (2013). Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis. Arthritis Research and Therapy, 15(2), doi:10.1186/ar4214
DOI https://doi.org/10.1186/ar4214
Publisher URL http://arthritis-research.com/content/15/2/R52
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
Additional Information Copy of License must accompany any deposit.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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