Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
권호 표지
DOI QR코드

DOI QR Code

Association Study of Fibroblast Growth Factor 2 and Fibroblast Growth Factor Receptors Gene Polymorphism in Korean Ossification of the Posterior Longitudinal Ligament Patients

  • Jun, Jae-Kyun (Department of Neurosurgery, Wooridul Spine Hospital) ;
  • Kim, Sung-Min (Department of Neurosurgery, School of Medicine, Kyung Hee University)
  • Received : 2011.09.05
  • Accepted : 2012.07.06
  • Published : 2012.07.28
Download PDF
⟨ Previous Next ⟩

Abstract

Objective : The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast growth factor receptor (FGFR) genes are associated with ossification of the posterior longitudinal ligament (OPLL). Methods : A total of 157 patients with OPLL and 222 controls were recruited for a case control association study investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395, rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793, rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Results : Of the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament flavum (OLF). Conclusion : The results of the present study revealed that an FGFR1 SNP was significantly associated with OPLL and that a SNP in FGF2 was associated with conditions that were comorbid with OPLL (DISH and OLF).

Keywords

References

  1. Chung WS, Nam DH, Jo DJ, Lee JH : Association of toll-like receptor 5 gene polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine in Koean population. J Korean Neurosurg Soc 49 : 8-12, 2011 https://doi.org/10.3340/jkns.2011.49.1.8
  2. Dunham-Ems SM, Lee YW, Stachowiak EK, Pudavar H, Claus P, Prasad PN, et al. : Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a novel mechanism in transcription control. Mol Biol Cell 20 : 2401-2412, 2009 https://doi.org/10.1091/mbc.E08-06-0600
  3. Ellman MB, An HS, Muddasani P, Im HJ : Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis. Gene 420 : 82-89, 2008 https://doi.org/10.1016/j.gene.2008.04.019
  4. Horikoshi T, Maeda K, Kawaguchi Y, Chiba K, Mori K, Koshizuka Y, et al. : A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. Hum Genet 119 : 611-616, 2006 https://doi.org/10.1007/s00439-006-0170-9
  5. Inamasu J, Guiot BH, Sachs DC : Ossification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history. Neurosurgery 58 : 1027-1039; discussion 1027-1039, 2006 https://doi.org/10.1227/01.NEU.0000215867.87770.73
  6. Key GA : On paraplegia depending on the ligament of the spine. Guy Hospital Report 3 : 17-34, 1839
  7. Kong Q, Ma X, Li F, Guo Z, Qi Q, Li W, et al. : COL6A1 polymorphisms associated with ossification of the ligamentum flavum and ossification of the posterior longitudinal ligament. Spine (Phila Pa 1976) 32 : 2834-2838, 2007 https://doi.org/10.1097/BRS.0b013e31815b761c
  8. Li H, Jiang LS, Dai LY : Hormones and growth factors in the pathogenesis of spinal ligament ossification. Eur Spine J 16 : 1075-1084, 2007 https://doi.org/10.1007/s00586-007-0356-4
  9. Marie PJ : Fibroblast growth factor signaling controlling osteoblast differentiation. Gene 316 : 23-32, 2003 https://doi.org/10.1016/S0378-1119(03)00748-0
  10. Katoh M: Cancer genomics and genetics of FGFR2 (Review). Int J Oncol 33 : 233-237, 2008
  11. Murakami M, Simons M : Fibroblast growth factor regulation of neovascularization. Curr Opin Hematol 15 : 215-220, 2008 https://doi.org/10.1097/MOH.0b013e3282f97d98
  12. Nakamura I, Ikegawa S, Okawa A, Okuda S, Koshizuka Y, Kawaguchi H, et al. : Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). Hum Genet 104 : 492-497, 1999 https://doi.org/10.1007/s004390050993
  13. Oppenheimer A : Calcification and ossification of vertebral ligaments (spondylitis ossificans ligamentosa). Radiology 38 : 160-173, 1942 https://doi.org/10.1148/38.2.160
  14. Sakou T, Matsunaga S, Koga H : Recent progress in the study of pathogenesis of ossification of the posterior longitudinal ligament. J Orthop Sci 5 : 310-315, 2000 https://doi.org/10.1007/s007760050169
  15. Tsukimoto H : [On an autopsied case of compression myelopathy with a callus formation in the cervical spinal canal]. Nihon-Geka-Hokan 29 : 1003-1007, 1960
  16. Wang H, Liu D, Yang Z, Tian B, Li J, Meng X, et al. : Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity in Chinese patients. Eur Spine J 17 : 956-964, 2008 https://doi.org/10.1007/s00586-008-0651-8

Cited by

  1. Diffuse idiopathic skeletal hyperostosis (Forestier-Rotes-Querol disease): What's new? vol.80, pp.5, 2013, https://doi.org/10.1016/j.jbspin.2013.02.011
  2. Genome-wide association study combined with biological context can reveal more disease-related SNPs altering microRNA target seed sites vol.15, pp.1, 2014, https://doi.org/10.1186/1471-2164-15-669
  3. A New Enpp1 allele, Enpp1 ttw-Ham , Identified in an ICR Closed Colony vol.63, pp.2, 2012, https://doi.org/10.1538/expanim.63.193
  4. Uniaxial Cyclic Stretch Promotes Osteogenic Differentiation and Synthesis of BMP2 in the C3H10T1/2 Cells with BMP2 Gene Variant of rs2273073 (T/G) vol.9, pp.9, 2012, https://doi.org/10.1371/journal.pone.0106598
  5. The Clinical Significance of Ossification of Ligamentum Nuchae in Simple Lateral Radiograph : A Correlation with Cervical Ossification of Posterior Longitudinal Ligament vol.58, pp.5, 2012, https://doi.org/10.3340/jkns.2015.58.5.442
  6. Pharmacogenetic analysis of cinacalcet response in secondary hyperparathyroidism patients vol.10, pp.None, 2012, https://doi.org/10.2147/dddt.s103370
  7. Targeted next-generation sequencing reveals multiple deleterious variants in OPLL-associated genes vol.6, pp.None, 2012, https://doi.org/10.1038/srep26962
  8. Increased Prevalence of Ossification of Posterior Longitudinal Ligament and Increased Bone Mineral Density in Patients with Ossification of Nuchal Ligament vol.13, pp.3, 2016, https://doi.org/10.14245/kjs.2016.13.3.139
  9. Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies vol.4, pp.None, 2012, https://doi.org/10.1038/hgv.2017.41
  10. The Pathogenesis of Ossification of the Posterior Longitudinal Ligament vol.8, pp.5, 2017, https://doi.org/10.14336/ad.2017.0201
  11. Myelopathy associated with instability consequent to resection of ossification of anterior longitudinal ligament in DISH vol.27, pp.None, 2018, https://doi.org/10.1007/s00586-017-5236-y
  12. Whole-genome sequencing reveals novel genes in ossification of the posterior longitudinal ligament of the thoracic spine in the Chinese population vol.13, pp.None, 2012, https://doi.org/10.1186/s13018-018-1022-8
  13. Cervical Ossification of the Posterior Longitudinal Ligament: A Computed Tomography-Based Epidemiological Study of 2917 Patients vol.9, pp.8, 2012, https://doi.org/10.1177/2192568219833658
  14. Polymorphisms of IRAK1 Gene on X Chromosome Is Associated with Hashimoto Thyroiditis in Korean Children vol.161, pp.8, 2020, https://doi.org/10.1210/endocr/bqaa088
  15. Diffuse Idiopathic Skeletal Hyperostosis (DISH) and a Possible Inflammatory Component vol.23, pp.1, 2021, https://doi.org/10.1007/s11926-020-00972-x
  16. Diffuse Idiopathic Skeletal Hyperostosis of Cervical Spine with Dysphagia—Molecular and Clinical Aspects vol.22, pp.8, 2012, https://doi.org/10.3390/ijms22084255
  17. Association between miRNA Target Sites and Incidence of Primary Osteoarthritis in Women from Volga-Ural Region of Russia: A Case-Control Study vol.11, pp.7, 2012, https://doi.org/10.3390/diagnostics11071222