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A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand

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Abstract

Objective

A number of studies have reported an association of GDF5 with osteoarthritis (OA) but have produced some divergent findings and their interpretation may not be straightforward.

Methods

We investigated the association between GDF5 and OA using meta-analytic techniques, combining all published data up to Nov 2014. 16 independent samples from 11 research teams contributed data on SNP rs143383 (located in the 5’-UTR of GDF5) and knee, hip, and hand OA. The total number of cases and controls for this marker was 7,965 and 12,747 for knee OA, 6,363 and 9,727 for hip OA, and 4,335 and 5,991 for hand OA, respectively. The ORs for each OA phenotype were synthesized using random-effects models or fixed-effects models depending on the test of between-study heterogeneity.

Results

Using a random-effect model, a significant difference was identified between patients with knee OA and controls for the T-allele of rs143383 (Subtotal OR = 1.18, 95 % CI=1.10–1.27, P=1.84 × 10-6). For hand OA, a moderate association was also observed (Subtotal OR = 1.09, 95 % CI = 1.02–1.16, P = 0.01) for SNP rs143383 in the combined population. However, non-statistically significant summary OR of hip OA was found in both combined studies (Subtotal OR = 1.22, 95 % CI = 0.97–1.53, P = 0.09) and European studies (Subtotal OR = 1.16, 95 % CI = 0.91–1.48, P = 0.23).

Conclusions

Our results demonstrate that SNP rs143383 of GDF5 is a compelling risk factor for both knee and hand OA, and provide further support for GDF5 in the etiology of OA. Further efforts to identify functional variants of GDF5 in in vitro and in vivo will be required.

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Acknowledgments

We are indebted to all the individuals who have participated in, or helped with, our research. This study was supported by the National Natural Science Foundation of China (No.81272023; No.81271948; No.81301151; No.31371298); China Postdoctoral Science Foundation (No.2013M542337); Program for New Century Excellent Talents in University (NCET-13-0452); the Key Project of International Scientific Cooperation of Shaanxi Province (No.S2013KW25-02); and the Fundamental Research Funds for the Central Universities (No.2012 JDGZ07; No.XJJ2012124).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, Shaanxi, China

    Rui Zhang, Shemin Lu & Jie Ma

  2. Xi’an Hong Hui Hospital, The Affiliated Hospital of Xi’an Jiaotong University Health Science Center, Xi’an, 710054, Shaanxi, China

    Rui Zhang, Jianfeng Yao & Peng Xu

  3. School of Medicine, University of California, San Diego, CA, 92093, USA

    Baohu Ji, Brian Chin, John R. Kelsoe & Jie Ma

  4. UCLA Orthopaedic Hospital Department of Orthopaedics, David Geffen School of Medicine, University of California at Los Angeles and Hemophilia Treatment Center, Orthopaedic Hospital, Los Angeles, CA, 90095, USA

    James V. Luck

  5. Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education, Xi’an, 710061, Shaanxi, China

    Jie Ma

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  1. Rui Zhang
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Correspondence to Jianfeng Yao or Jie Ma.

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Zhang, R., Yao, J., Xu, P. et al. A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand. Inflamm. Res. 64, 405–414 (2015). https://doi.org/10.1007/s00011-015-0818-9

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  • DOI: https://doi.org/10.1007/s00011-015-0818-9

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