Top

Journal of Orthopaedic Surgery and Research

Published in:

Open Access 01-12-2016 | Research article

Association between GDF5 +104T/C polymorphism and knee osteoarthritis in Caucasian and Asian populations: a meta-analysis based on case-control studies

Authors: Dong Jiang, Zengtao Hao, Dongsheng Fan, Wen Guo, Pengcheng Xu, Chao Yin, Shuzheng Wen, Jihong Wang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2016

Abstract

Background

Osteoarthritis (OA) is a degenerative joint disease with a complex genetic background. Variants in growth differentiation factor 5 (GDF5) have been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The present study aimed to assess the association between the GDF5 +104T/C polymorphism and the susceptibility of the knee to OA through a meta-analysis of available case-control studies.

Methods

The PubMed and Science Direct citation databases were used to search electronic literature in order to identify studies published between January 2007 and July 2016 that evaluated the association between the GDF5 +104T/C polymorphism and the susceptibility of the knee to OA. Different genetic models were used to assess the pooled and stratified data.

Results

A positive association was found in all pooled studies (OR = 0.808, 95 % CI = 0.754–0.866, p < 0.001). Regarding genotypes, significant associations were found using a dominant model (OR = 0.777, 95 % CI = 0.708–0.852, p < 0.001), a recessive model (OR = 0.723, 95%CI = 0.623–0.839, p < 0.001), and an additive model (CC vs TT OR = 0.648, 95 % CI = 0.552–0.760, p < 0.001; CC vs CT OR = 0.801, 95 % CI = 0.685–0.936, p = 0.005). Meta-analysis data were stratified by ethnicity, and the GDF5 C allele was found to be positively associated with OA of the knee in both Caucasians and Asians, as were the GDF5 TC and CC genotypes. In addition, using an additive model, the CC genotype was found to be significantly associated with OA of the knee in both Caucasians and Asians when comparing CC vs TT genotypes, but not in Caucasians when comparing TT vs CT genotypes.

Conclusions

Meta-analysis results indicated that the GDF5 +104T/C polymorphism is a protective factor for OA among Caucasian and Asian populations.

Murphy L, Helmick CG. The impact of osteoarthritis in the United States: a population-health perspective. Am J Nurs. 2012;112:S13–19.CrossRefPubMed

O'Conor CJ, Ramalingam S, Zelenski NA, Benefield HC, Rigo I, Little D, Wu CL, Chen D, Liedtke W, McNulty AL, Guilak F. Cartilage-specific knockout of the mechanosensory ion channel TRPV4 decreases age-related osteoarthritis. Sci Rep. 2016;6:29053.CrossRefPubMedPubMedCentral

Guilak F. Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 2011;25:815–23.CrossRefPubMedPubMedCentral

van Tunen JA, Dell'Isola A, Juhl C, Dekker J, Steultjens M, Lund H. Biomechanical factors associated with the development of tibiofemoral knee osteoarthritis: protocol for a systematic review and meta-analysis. BMJ Open. 2016;6:e011066.CrossRefPubMedPubMedCentral

Hochberg MC, Yerges-Armstrong L, Yau M, Mitchell BD. Genetic epidemiology of osteoarthritis: recent developments and future directions. Curr Opin Rheumatol. 2013;25:192–7.CrossRefPubMedPubMedCentral

Loughlin J. The genetic epidemiology of human primary osteoarthritis: current status. Expert Rev Mol Med. 2005;7:1–12.CrossRefPubMed

MacGregor AJ, Li Q, Spector TD, Williams FM. The genetic influence on radiographic osteoarthritis is site specific at the hand, hip and knee. Rheumatology (Oxford). 2009;48:277–80.CrossRef

Vincent TL. Targeting mechanotransduction pathways in osteoarthritis: a focus on the pericellular matrix. Curr Opin Pharmacol. 2013;13:449–54.CrossRefPubMed

Martinez-Garcia M, Garcia-Canto E, Fenollar-Cortes M, Aytes AP, Trujillo-Tiebas MJ. Characterization of an acromesomelic dysplasia, Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5. J Bone Miner Metab. 2015. doi:10.1007/s00774-015-0693-z.PubMed

10.

Al-Qattan MM, Al-Motairi MI, Al Balwi MA. Two novel homozygous missense mutations in the GDF5 gene cause brachydactyly type C. Am J Med Genet A. 2015;167:1621–6.CrossRefPubMed

11.

Farooq M, Nakai H, Fujimoto A, Fujikawa H, Kjaer KW, Baig SM, Shimomura Y. Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family. Hum Genet. 2013;132:1253–64.CrossRefPubMed

12.

Khan S, Basit S, Khan MA, Muhammad N, Ahmad W. Genetics of human isolated acromesomelic dysplasia. Eur J Med Genet. 2016;59:198–203.CrossRefPubMed

13.

Zhang R, Yao J, Xu P, Ji B, Luck JV, Chin B, Lu S, Kelsoe JR, Ma J. A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand. Inflamm Res. 2015;64:405–14.CrossRefPubMed

14.

Pan F, Tian J, Winzenberg T, Ding C, Jones G. Association between GDF5 rs143383 polymorphism and knee osteoarthritis: an updated meta-analysis based on 23,995 subjects. BMC Musculoskelet Disord. 2014;15:404.CrossRefPubMedPubMedCentral

15.

Liu J, Cai W, Zhang H, He C, Deng L. Rs143383 in the growth differentiation factor 5 (GDF5) gene significantly associated with osteoarthritis (OA)-a comprehensive meta-analysis. Int J Med Sci. 2013;10:312–9.CrossRefPubMedPubMedCentral

16.

Xiao JL, Meng JH, Gan YH, Zhou CY, Ma XC. Association of GDF5, SMAD3 and RUNX2 polymorphisms with temporomandibular joint osteoarthritis in female Han Chinese. J Oral Rehabil. 2015;42:529–36.CrossRefPubMed

17.

Mishra A, Sanghi D, Maurya SS, Singh A, Srivastava RN, Sharma C, Raj S, Avasthi S, Parmar D. Association of polymorphism in growth and differentiation factor 5 gene with osteoarthritis knee. American Journal of Biochemistry & Biotechnology. 2013. doi:10.1186/1471-2474-15-404.

18.

Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.CrossRef

19.

Dersimonian R, Nan L. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMed

20.

Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.CrossRefPubMed

21.

Patsopoulos NA, Evangelou E, Ioannidis JP. Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol. 2008;37:1148–57.CrossRefPubMed

22.

Thakkinstian A, McElduff P, D'Este C, Duffy D, Attia J. A method for meta-analysis of molecular association studies. Stat Med. 2005;24:1291–306.CrossRefPubMed

23.

Song F, Gilbody S. Bias in meta-analysis detected by a simple, graphical test. Increase in studies of publication bias coincided with increasing use of meta-analysis. BMJ. 1998;316:471.PubMedPubMedCentral

24.

Miyamoto Y, Mabuchi A, Shi D, Kubo T, Takatori Y, Saito S, Fujioka M, Sudo A, Uchida A, Yamamoto S, Ozaki K, Takigawa M, Tanaka T, Nakamura Y, Jiang Q, Ikegawa S. A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet. 2007;39:529–33.CrossRefPubMed

25.

Southam L, Rodriguez-Lopez J, Wilkins JM, Pombo-Suarez M, Snelling S, Gomez-Reino JJ, Chapman K, Gonzalez A, Loughlin J. An SNP in the 5′-UTR of GDF5 is associated with osteoarthritis susceptibility in Europeans and with in vivo differences in allelic expression in articular cartilage. Hum Mol Genet. 2007;16:2226–32.CrossRefPubMed

26.

Tawonsawatruk T, Changthong T, Pingsuthiwong S, Trachoo O, Sura T, Wajanavisit W. A genetic association study between growth differentiation factor 5 (GDF 5) polymorphism and knee osteoarthritis in Thai population. J Orthop Surg Res. 2011;6:47.CrossRefPubMedPubMedCentral

27.

Tsezou A, Satra M, Oikonomou P, Bargiotas K, Malizos KN. The growth differentiation factor 5 (GDF5) core promoter polymorphism is not associated with knee osteoarthritis in the Greek population. J Orthop Res. 2008;26:136–40.CrossRefPubMed

28.

Valdes AM, Spector TD, Doherty S, Wheeler M, Hart DJ, Doherty M. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann Rheum Dis. 2009;68:1916–20.CrossRefPubMed

29.

Cao Z, Lee HS, Song JH, Yoon JW, Yong KP, Nam SW, Lee JY, Park WS. Growth differentiation factor 5 (GDF5) core promoter polymorphism is not associated with susceptibility to osteoarthritis of the knee in the Korean population. Korean J Pathol. 2010;44:404–9.CrossRef

30.

Francis-West PH, Abdelfattah A, Chen P, Allen C, Parish J, Ladher R, Allen S, MacPherson S, Luyten FP, Archer CW. Mechanisms of GDF-5 action during skeletal development. Development. 1999;126:1305–15.PubMed

31.

Gallagher JA, Ranganath LR, Boyde A. Lessons from rare diseases of cartilage and bone. Curr Opin Pharmacol. 2015;22:107–14.CrossRefPubMed

32.

Reynard LN, Loughlin J. The genetics and functional analysis of primary osteoarthritis susceptibility. Expert Rev Mol Med. 2013;15:e2.CrossRefPubMedPubMedCentral

33.

Ohta Y, Okabe T, Larmour C, Di Rocco A, Maijenburg MW, Phillips A, Speck NA, Wakitani S, Nakamura T, Yamada Y, Enomoto-Iwamoto M, Pacifici M, Iwamoto M. Articular cartilage endurance and resistance to osteoarthritic changes require transcription factor Erg. Arthritis Rheumatol. 2015;67:2679–90.CrossRefPubMed

34.

Lee M, Aggen SH, Otowa T, Castelao E, Preisig M, Grabe HJ, Hartman CA, Oldehinkel AJ, Middeldorp CM, Tiemeier H, Hettema JM. Assessment and characterization of phenotypic heterogeneity of anxiety disorders across five large cohorts. Int J Methods Psychiatr Res. 2016. doi:10.1002/mpr.1519.PubMed

35.

Evangelou E, Chapman K, Meulenbelt I, Karassa FB, Loughlin J, Carr A, Doherty M, Doherty S, Gomez-Reino JJ, Gonzalez A, Halldorsson BV, Hauksson VB, Hofman A, Hart DJ, Ikegawa S, Ingvarsson T, Jiang Q, Jonsdottir I, Jonsson H, Kerkhof HJ, Kloppenburg M, Lane NE, Li J, Lories RJ, van Meurs JB, Nakki A, Nevitt MC, Rodriguez-Lopez J, Shi D, Slagboom PE, Stefansson K, Tsezou A, Wallis GA, Watson CM, Spector TD, Uitterlinden AG, Valdes AM, Ioannidis JP. Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand. Arthritis Rheum. 2009;60:1710–21.CrossRefPubMedPubMedCentral

Title: Association between GDF5 +104T/C polymorphism and knee osteoarthritis in Caucasian and Asian populations: a meta-analysis based on case-control studies
Authors: Dong Jiang
Zengtao Hao
Dongsheng Fan
Wen Guo
Pengcheng Xu
Chao Yin
Shuzheng Wen
Jihong Wang
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2016
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-016-0436-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Association between GDF5 +104T/C polymorphism and knee osteoarthritis in Caucasian and Asian populations: a meta-analysis based on case-control studies

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Kinematics of anterior cruciate ligament-deficient knees in a Chinese population during stair ascent

Biological and functional evaluation of a novel pyrolytic carbon implant for the treatment of focal osteochondral defects in the medial femoral condyle: assessment in a canine model

Interleukin-23 may contribute to the pathogenesis of lumbar disc herniation through the IL-23/IL-17 pathway

Kinematic analysis of posterior-stabilized total knee arthroplasty during standing up from and sitting down on a chair

A retrospective analysis of the InterTan nail and proximal femoral nail anti-rotation-Asia in the treatment of unstable intertrochanteric femur fractures in the elderly

RETRACTED ARTICLE: Minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review of overlapping meta-analyses