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Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis
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Muthuri, Stella G., Doherty, Sally A., Zhang, Weiya, Maciewicz, Rose A., Muir, Kenneth and Doherty, Michael (2013) Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFβ1) gene in knee and hip osteoarthritis. Arthritis Research & Therapy, Volume 15 (Number 2). Article number R52. doi:10.1186/ar4214 ISSN 1478-6354.
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Official URL: http://dx.doi.org/10.1186/ar4214
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
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Osteoarthritis -- Genetic aspects, Body mass index, Transforming growth factors-beta | ||||||||
| Journal or Publication Title: | Arthritis Research & Therapy | ||||||||
| Publisher: | BioMed Central Ltd. | ||||||||
| ISSN: | 1478-6354 | ||||||||
| Official Date: | 18 April 2013 | ||||||||
| Dates: |
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| Volume: | Volume 15 | ||||||||
| Number: | Number 2 | ||||||||
| Article Number: | Article number R52 | ||||||||
| DOI: | 10.1186/ar4214 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 27 December 2015 | ||||||||
| Date of first compliant Open Access: | 27 December 2015 | ||||||||
| Funder: | AstraZeneca (Firm), Arthritis Research UK | ||||||||
| Grant number: | 14851 (ARUK) |
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