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Erschienen in: European Spine Journal 3/2014

01.03.2014 | Original Article

A SNP in the 5′UTR of GDF5 is associated with susceptibility to symptomatic lumbar disc herniation in the Chinese Han population

verfasst von: Jihong Mu, Weiming Ge, Xincheng Zuo, Yuxuan Chen, Changlin Huang

Erschienen in: European Spine Journal | Ausgabe 3/2014

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Abstract

Purpose

The aim of the present study is to assess whether the single nucleotide polymorphism in the GDF5 (+104T/C; rs143383) is associated with the symptomatic lumbar disc herniation in the Chinese Han population and the identification of the mechanisms of its action.

Methods

This study consisted of 231 patients with symptomatic lumbar disc herniation as the case group and 370 patients who had a lifetime lack of symptoms as the control group. PCR products were genotyped. Thirty-eight disc specimens derived from the cases were analyzed by immunohistochemical staining. The stain intensity of immunohistochemistry was quantified using a computerized image analysis system.

Results

Significant differences in genotypic and allelic frequencies were found between case group and control group (TT genotype P < 0.001; CC genotype P = 0.002; T allele P < 0.001). The T allele was more frequent in the case group regardless of gender (Female P = 0.018; Male P < 0.001). Significant differences were found in the genotype frequencies when stratified by gender except the comparison between the CC genotype and other genotypes combined among the female samples (P > 0.05). A semi-quantification of collagen protein in the nucleus pulposus showed that the average collagen protein content in TC group was higher than in TT group (P < 0.05).

Conclusion

Our results suggested that the GDF5 polymorphism is associated with a susceptibility to symptomatic lumbar disc herniation in the Chinese Han population and type II collagen in the nucleus pulposus may be a key factor in susceptibility to symptomatic lumbar disc herniation.
Literatur
1.
Zurück zum Zitat Kuh DJ, Coggan D, Mann S, Cooper C, Yusuf E (1993) Height, occupation and back pain in a national prospective study. Br J Rheumatol 32:911–916PubMedCrossRef Kuh DJ, Coggan D, Mann S, Cooper C, Yusuf E (1993) Height, occupation and back pain in a national prospective study. Br J Rheumatol 32:911–916PubMedCrossRef
2.
Zurück zum Zitat Battie MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K, 1995 Volvo Award in clinical sciences (1995) Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine (Phila Pa 1976) 20:2601–2612CrossRef Battie MC, Videman T, Gibbons LE, Fisher LD, Manninen H, Gill K, 1995 Volvo Award in clinical sciences (1995) Determinants of lumbar disc degeneration. A study relating lifetime exposures and magnetic resonance imaging findings in identical twins. Spine (Phila Pa 1976) 20:2601–2612CrossRef
3.
Zurück zum Zitat Battie MC, Videman T, Levalahti E, Gill K, Kaprio J (2008) Genetic and environmental effects on disc degeneration by phenotype and spinal level: a multivariate twin study. Spine (Phila Pa 1976) 33:2801–2808CrossRef Battie MC, Videman T, Levalahti E, Gill K, Kaprio J (2008) Genetic and environmental effects on disc degeneration by phenotype and spinal level: a multivariate twin study. Spine (Phila Pa 1976) 33:2801–2808CrossRef
5.
Zurück zum Zitat Paz Aparicio J, Fernandez Bances I, Lopez-Anglada Fernandez E, Montes AH, Paz Aparicio A, Pena Vazquez J, Ramos Garcia S, Anton Garcia S, Lopez Fernandez P, Valle-Garay E, Asensi V (2011) The IL-1beta (+3953 T/C) gene polymorphism associates to symptomatic lumbar disc herniation. Eur Spine J 20(Suppl 3):383–389PubMedCentralPubMedCrossRef Paz Aparicio J, Fernandez Bances I, Lopez-Anglada Fernandez E, Montes AH, Paz Aparicio A, Pena Vazquez J, Ramos Garcia S, Anton Garcia S, Lopez Fernandez P, Valle-Garay E, Asensi V (2011) The IL-1beta (+3953 T/C) gene polymorphism associates to symptomatic lumbar disc herniation. Eur Spine J 20(Suppl 3):383–389PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Mikic B (2004) Multiple effects of GDF-5 deficiency on skeletal tissues: implications for therapeutic bioengineering. Ann Biomed Eng 32:466–476PubMedCrossRef Mikic B (2004) Multiple effects of GDF-5 deficiency on skeletal tissues: implications for therapeutic bioengineering. Ann Biomed Eng 32:466–476PubMedCrossRef
7.
Zurück zum Zitat Francis-West PH, Abdelfattah A, Chen P, Allen C, Parish J, Ladher R, Allen S, MacPherson S, Luyten FP, Archer CW (1999) Mechanisms of GDF-5 action during skeletal development. Development 126:1305–1315PubMed Francis-West PH, Abdelfattah A, Chen P, Allen C, Parish J, Ladher R, Allen S, MacPherson S, Luyten FP, Archer CW (1999) Mechanisms of GDF-5 action during skeletal development. Development 126:1305–1315PubMed
8.
Zurück zum Zitat Edwards CJ, Francis-West PH (2001) Bone morphogenetic proteins in the development and healing of synovial joints. Semin Arth Rheum 31:33–42CrossRef Edwards CJ, Francis-West PH (2001) Bone morphogenetic proteins in the development and healing of synovial joints. Semin Arth Rheum 31:33–42CrossRef
9.
Zurück zum Zitat Luyten FP (1997) Cartilage-derived morphogenetic protein-1. Int J Biochem Cell Biol 29:1241–1244PubMedCrossRef Luyten FP (1997) Cartilage-derived morphogenetic protein-1. Int J Biochem Cell Biol 29:1241–1244PubMedCrossRef
10.
Zurück zum Zitat Harada M, Takahara M, Zhe P, Otsuji M, Iuchi Y, Takagi M, Ogino T (2007) Developmental failure of the intra-articular ligaments in mice with absence of growth differentiation factor 5. Osteoarth Cartil 15:468–474CrossRef Harada M, Takahara M, Zhe P, Otsuji M, Iuchi Y, Takagi M, Ogino T (2007) Developmental failure of the intra-articular ligaments in mice with absence of growth differentiation factor 5. Osteoarth Cartil 15:468–474CrossRef
11.
Zurück zum Zitat Vaes RB, Rivadeneira F, Kerkhof JM, Hofman A, Pols HA, Uitterlinden AG, van Meurs JB (2009) Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study. Ann Rheum Dis 68:1754–1760PubMedCrossRef Vaes RB, Rivadeneira F, Kerkhof JM, Hofman A, Pols HA, Uitterlinden AG, van Meurs JB (2009) Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study. Ann Rheum Dis 68:1754–1760PubMedCrossRef
12.
Zurück zum Zitat 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 (2008) Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Gen 40:198–203CrossRef 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 (2008) Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Gen 40:198–203CrossRef
13.
Zurück zum Zitat Le Maitre CL, Pockert A, Buttle DJ, Freemont AJ, Hoyland JA (2007) Matrix synthesis and degradation in human intervertebral disc degeneration. Biochem Soc Trans 35:652–655PubMedCrossRef Le Maitre CL, Pockert A, Buttle DJ, Freemont AJ, Hoyland JA (2007) Matrix synthesis and degradation in human intervertebral disc degeneration. Biochem Soc Trans 35:652–655PubMedCrossRef
14.
Zurück zum Zitat Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 20:1307–1314 Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976) 20:1307–1314
15.
Zurück zum Zitat Bai X, Xiao Z, Pan Y, Hu J, Pohl J, Wen J, Li L (2004) Cartilage-derived morphogenetic protein-1 promotes the differentiation of mesenchymal stem cells into chondrocytes. Biochem Biophys Res Comm 325:453–460PubMedCrossRef Bai X, Xiao Z, Pan Y, Hu J, Pohl J, Wen J, Li L (2004) Cartilage-derived morphogenetic protein-1 promotes the differentiation of mesenchymal stem cells into chondrocytes. Biochem Biophys Res Comm 325:453–460PubMedCrossRef
16.
Zurück zum Zitat 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 (2007) A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Gen 39:529–533CrossRef 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 (2007) A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Gen 39:529–533CrossRef
17.
Zurück zum Zitat 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 (2008) 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 Gen 17:1497–1504PubMedCrossRef 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 (2008) 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 Gen 17:1497–1504PubMedCrossRef
18.
Zurück zum Zitat Southam L, Rodriguez-Lopez J, Wilkins JM, Pombo-Suarez M, Snelling S, Gomez-Reino JJ, Chapman K, Gonzalez A, Loughlin J (2007) 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 Gen 16:2226–2232PubMedCrossRef Southam L, Rodriguez-Lopez J, Wilkins JM, Pombo-Suarez M, Snelling S, Gomez-Reino JJ, Chapman K, Gonzalez A, Loughlin J (2007) 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 Gen 16:2226–2232PubMedCrossRef
19.
Zurück zum Zitat Tsezou A, Satra M, Oikonomou P, Bargiotas K, Malizos KN (2008) The growth differentiation factor 5 (GDF5) core promoter polymorphism is not associated with knee osteoarthritis in the Greek population. J Orthop Res 26:136–140PubMedCrossRef Tsezou A, Satra M, Oikonomou P, Bargiotas K, Malizos KN (2008) The growth differentiation factor 5 (GDF5) core promoter polymorphism is not associated with knee osteoarthritis in the Greek population. J Orthop Res 26:136–140PubMedCrossRef
20.
Zurück zum Zitat Williams FM, Popham M, Hart DJ, de Schepper E, Bierma-Zeinstra S, Hofman A, Uitterlinden AG, Arden NK, Cooper C, Spector TD, Valdes AM, van Meurs J (2011) GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women. Arth Rheum 63:708–712CrossRef Williams FM, Popham M, Hart DJ, de Schepper E, Bierma-Zeinstra S, Hofman A, Uitterlinden AG, Arden NK, Cooper C, Spector TD, Valdes AM, van Meurs J (2011) GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women. Arth Rheum 63:708–712CrossRef
21.
Zurück zum Zitat Dai J, Shi D, Zhu P, Qin J, Ni H, Xu Y, Yao C, Zhu L, Zhu H, Zhao B, Wei J, Liu B, Ikegawa S, Jiang Q, Ding Y (2008) Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: a case-control study. Arth Res Ther 10:R126CrossRef Dai J, Shi D, Zhu P, Qin J, Ni H, Xu Y, Yao C, Zhu L, Zhu H, Zhao B, Wei J, Liu B, Ikegawa S, Jiang Q, Ding Y (2008) Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: a case-control study. Arth Res Ther 10:R126CrossRef
22.
Zurück zum Zitat Egli RJ, Southam L, Wilkins JM, Lorenzen I, Pombo-Suarez M, Gonzalez A, Carr A, Chapman K, Loughlin J (2009) Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism. Arth Rheum 60:2055–2064CrossRef Egli RJ, Southam L, Wilkins JM, Lorenzen I, Pombo-Suarez M, Gonzalez A, Carr A, Chapman K, Loughlin J (2009) Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism. Arth Rheum 60:2055–2064CrossRef
23.
Zurück zum Zitat Valdes AM, Spector TD, Doherty S, Wheeler M, Hart DJ, Doherty M (2009) Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann Rheum Dis 68:1916–1920PubMedCrossRef Valdes AM, Spector TD, Doherty S, Wheeler M, Hart DJ, Doherty M (2009) Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann Rheum Dis 68:1916–1920PubMedCrossRef
24.
Zurück zum Zitat Rouault K, Scotet V, Autret S, Gaucher F, Dubrana F, Tanguy D, El Rassi CY, Fenoll B, Ferec C (2010) Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a caucasian population. Osteoarth Cartil 18:1144–1149CrossRef Rouault K, Scotet V, Autret S, Gaucher F, Dubrana F, Tanguy D, El Rassi CY, Fenoll B, Ferec C (2010) Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a caucasian population. Osteoarth Cartil 18:1144–1149CrossRef
25.
Zurück zum Zitat Henn RF 3rd, Kuo CE, Kessler MW, Razzano P, Grande DP, Wolfe SW (2010) Augmentation of zone II flexor tendon repair using growth differentiation factor 5 in a rabbit model. J Hand Surg Am 35:1825–1832PubMedCrossRef Henn RF 3rd, Kuo CE, Kessler MW, Razzano P, Grande DP, Wolfe SW (2010) Augmentation of zone II flexor tendon repair using growth differentiation factor 5 in a rabbit model. J Hand Surg Am 35:1825–1832PubMedCrossRef
26.
Zurück zum Zitat Le Maitre CL, Freemont AJ, Hoyland JA (2009) Expression of cartilage-derived morphogenetic protein in human intervertebral discs and its effect on matrix synthesis in degenerate human nucleus pulposus cells. Arth Res Ther 11:R137CrossRef Le Maitre CL, Freemont AJ, Hoyland JA (2009) Expression of cartilage-derived morphogenetic protein in human intervertebral discs and its effect on matrix synthesis in degenerate human nucleus pulposus cells. Arth Res Ther 11:R137CrossRef
Metadaten
Titel
A SNP in the 5′UTR of GDF5 is associated with susceptibility to symptomatic lumbar disc herniation in the Chinese Han population
verfasst von
Jihong Mu
Weiming Ge
Xincheng Zuo
Yuxuan Chen
Changlin Huang
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Spine Journal / Ausgabe 3/2014
Print ISSN: 0940-6719
Elektronische ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-013-3059-z

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