Int J Sports Med 2014; 35(07): 625-628
DOI: 10.1055/s-0033-1355417
Genetics & Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

The GDF5 SNP is Associated with Meniscus Injury and Function Recovery in Male Chinese Soldiers

W. Ge
1   Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
,
J. Mu
1   Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
,
C. Huang
2   Institute of Military Training Related Medical Sciences, the 150 Hospital of Chinese PLA, Luoyang, Henan, P. R. China
› Author Affiliations
Further Information

Publication History



accepted after revision 19 August 2013

Publication Date:
13 November 2013 (online)

Abstract

Genetic factor have previously been shown to play an important role in sports injuries and recovery. GDF5 Single-Nucleotide Polymorphism rs143383 has been recently reported to be associated with fracture susceptibility. Furthermore, the effect of GDF5 during the recovery processes of trauma is increased. In the present study, we aimed to evaluate whether this SNP was associated with susceptibility to the meniscus injury and postoperative recovery in Chinese male soldiers. GDF5 SNP was genotyped in 135 male soldiers with meniscus injury and 400 healthy male controls. Moreover, the function recovery of the soldiers suffering from the meniscal repair was also assessed. Our data showed that the GDF5 TT genotype (60.0 vs. 47.25%; P=0.010) and T allele (76.3 vs. 68.75%; P=0.019) were significantly over-represented in the meniscus injury group compared with the control group. We found that the TC (P<0.05), CC (P<0.05) and C carriers (P<0.05) genotype exhibited significantly higher Lysholm Scores than the TT genotype at 1 month postoperative. In addition, the CC (P<0.05) genotype also demonstrated significantly higher Lysholm Scores than the TT genotype 2 months postoperative. Taken together, our results revealed that the GDF5 SNP was associated with susceptibility to the meniscus injury and postoperative function recovery in Chinese male soldiers.

 
  • References

  • 1 Bobacz K, Gruber R, Soleiman A, Graninger WB, Luyten FP, Erlacher L. Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis. Osteoarthrit Cartil 2002; 10: 394-401
  • 2 Buxton P, Edwards C, Archer CW, Francis-West P. Growth/differentiation factor-5 (GDF-5) and skeletal development. J Bone Joint Surg Am 2001; 83-A (Suppl. 01) S23-S30
  • 3 Chang SC, Hoang B, Thomas JT, Vukicevic S, Luyten FP, Ryba NJ, Kozak CA, Reddi AH, Moos Jr M. Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development. J Biol Chem 1994; 269: 28227-28234
  • 4 Chapman K, Takahashi A, Meulenbelt I, Watson C, Rodriguez-Lopez J, Egli R, Tsezou A, Malizos KN, Kloppenburg M, Shi D, Southam L, van der Breggen R, Donn R, Qin J, Doherty M, Slagboom PE, Wallis G, Kamatani N, Jiang Q, Gonzalez A, Loughlin J, Ikegawa S. A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5′ UTR of GDF5 with osteoarthritis susceptibility. Hum Mol Genet 2008; 17: 1497-1504
  • 5 Chhabra A, Tsou D, Clark RT, Gaschen V, Hunziker EB, Mikic B. GDF-5 deficiency in mice delays Achilles tendon healing. J Orthop Res 2003; 21: 826-835
  • 6 Chhabra A, Zijerdi D, Zhang J, Kline A, Balian G, Hurwitz S. BMP-14 deficiency inhibits long bone fracture healing: a biochemical, histologic, and radiographic assessment. J Orthop Trauma 2005; 19: 629-634
  • 7 Coleman CM, Tuan RS. Functional role of growth/differentiation factor 5 in chondrogenesis of limb mesenchymal cells. Mech Dev 2003; 120: 823-836
  • 8 Erlacher L, McCartney J, Piek E, ten Dijke P, Yanagishita M, Oppermann H, Luyten FP. Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis. J Bone Miner Res 1998; 13: 383-392
  • 9 Erlacher L, Ng CK, Ullrich R, Krieger S, Luyten FP. Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro. Arthritis Rheum 1998; 41: 263-273
  • 10 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: 1305-1315
  • 11 Harriss DJ, Atkinson G. Update – Ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
  • 12 Hotten GC, Matsumoto T, Kimura M, Bechtold RF, Kron R, Ohara T, Tanaka H, Satoh Y, Okazaki M, Shirai T, Pan H, Kawai S, Pohl JS, Kudo A. Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs. Growth Factors 1996; 13: 65-74
  • 13 Lysholm J, Gillquist J. Evaluation of knee ligament surgery results with special emphasis on use of a scoring scale. Am J Sports Med 1982; 10: 150-154
  • 14 Masuya H, Nishida K, Furuichi T, Toki H, Nishimura G, Kawabata H, Yokoyama H, Yoshida A, Tominaga S, Nagano J, Shimizu A, Wakana S, Gondo Y, Noda T, Shiroishi T, Ikegawa S. A novel dominant-negative mutation in Gdf5 generated by ENU mutagenesis impairs joint formation and causes osteoarthritis in mice. Hum Mol Genet 2007; 16: 2366-2375
  • 15 Mikic B. Multiple effects of GDF-5 deficiency on skeletal tissues: implications for therapeutic bioengineering. Ann Biomed Eng 2004; 32: 466-476
  • 16 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: 529-533
  • 17 Ploger F, Seemann P, Schmidt-von Kegler M, Lehmann K, Seidel J, Kjaer KW, Pohl J, Mundlos S. Brachydactyly type A2 associated with a defect in proGDF5 processing. Hum Mol Genet 2008; 17: 1222-1233
  • 18 Polinkovsky A, Robin NH, Thomas JT, Irons M, Lynn A, Goodman FR, Reardon W, Kant SG, Brunner HG, van der Burgt I, Chitayat D, McGaughran J, Donnai D, Luyten FP, Warman ML. Mutations in CDMP1 cause autosomal dominant brachydactyly type C. Nat Genet 1997; 17: 18-19
  • 19 Posthumus M, Collins M, Cook J, Handley CJ, Ribbans WJ, Smith RK, Schwellnus MP, Raleigh SM. Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology-a genetic association study. Rheumatology (Oxford) 2010; 49: 2090-2097
  • 20 Rickert M, Wang H, Wieloch P, Lorenz H, Steck E, Sabo D, Richter W. Adenovirus-mediated gene transfer of growth and differentiation factor-5 into tenocytes and the healing rat Achilles tendon. Connect Tissue Res 2005; 46: 175-183
  • 21 Sanna S, Jackson AU, Nagaraja R, Willer CJ, Chen WM, Bonnycastle LL, Shen H, Timpson N, Lettre G, Usala G, Chines PS, Stringham HM, Scott LJ, Dei M, Lai S, Albai G, Crisponi L, Naitza S, Doheny KF, Pugh EW, Ben-Shlomo Y, Ebrahim S, Lawlor DA, Bergman RN, Watanabe RM, Uda M, Tuomilehto J, Coresh J, Hirschhorn JN, Shuldiner AR, Schlessinger D, Collins FS, Davey Smith G, Boerwinkle E, Cao A, Boehnke M, Abecasis GR, Mohlke KL. Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet 2008; 40: 198-203
  • 22 Savarirayan R, White SM, Goodman FR, Graham Jr JM, Delatycki MB, Lachman RS, Rimoin DL, Everman DB, Warman ML. Broad phenotypic spectrum caused by an identical heterozygous CDMP-1 mutation in three unrelated families. Am J Med Genet A 2003; 117A: 136-142
  • 23 Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, Stricker S, Pohl J, Ploger F, Staub E, Nickel J, Sebald W, Knaus P, Mundlos S. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J Clin Invest 2005; 115: 2373-2381
  • 24 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: 2226-2232
  • 25 Storm EE, Kingsley DM. GDF5 coordinates bone and joint formation during digit development. Dev Biol 1999; 209: 11-27
  • 26 Tashiro T, Hiraoka H, Ikeda Y, Ohnuki T, Suzuki R, Ochi T, Nakamura K, Fukui N. Effect of GDF-5 on ligament healing. J Orthop Res 2006; 24: 71-79
  • 27 Vaes RB, Rivadeneira F, Kerkhof JM, Hofman A, Pols HA, Uitterlinden AG, van Meurs JB. Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study. Ann Rheum Dis 2009; 68: 1754-1760
  • 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: 1916-1920
  • 29 Walsh AJ, Bradford DS, Lotz JC. In vivo growth factor treatment of degenerated intervertebral discs. Spine 2004; 29: 156-163
  • 30 Williams FM, Popham M, Hart DJ, Deschepper E, Bierma-Zeinstra S, Hofman A, Uitterlinden AG, Arden NK, Cooper C, Spector TD, Valdes AM, Vanmeurs J. GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women. Arthritis Rheum 2011; 63: 708-712