Top

European Spine Journal

Published in:

01-01-2014 | Original Article

Progression of lumbar spinal stenosis is influenced by polymorphism of thrombospondin 2 gene in the Korean population

Authors: Seung-Jae Hyun, Borae G. Park, Seung-Chul Rhim, Jun-Won Jang, Sang-Ryong Jeon, Sung-Woo Roh

Published in: European Spine Journal | Issue 1/2014

Abstract

Purpose

The aim of this study is to determine the contribution of thrombospondin 2 (THBS2) polymorphisms to the development and progression of lumbar spinal stenosis (LSS) in the Korean population.

Methods

We studied 148 symptomatic patients with radiographically proven LSS and 157 volunteers with no history of back problems from our institution. Magnetic resonance images were obtained for all the patients and controls. Quantitative image evaluation for LSS was performed to evaluate the severity of LSS. All patients and controls were genotyped for THBS2 allele variations using a polymerase chain reaction-based technique.

Results

We found no causal single nucleotide polymorphism (SNPs) in THBS2 that were significantly associated with LSS. Two SNPs (rs6422747, rs6422748) were over-represented in controls [P = 0.042, odds ratio [OR] = 0.55 and P = 0.042, OR = 0.55, respectively]. Haplotype analysis showed that the ‘‘AGAGACG’’ haplotype (HAP4) and ‘‘AAGGACG’’ haplotype (HAP5) were over-represented in severe LSS patients (P = 0.0147, OR = 2.02 and P = 0.0137, OR = 2.48, respectively). In addition, the ‘‘AAAGGGG’’ haplotype (HAP1) was over-represented in controls (P = 0.0068, OR = 0.30).

Conclusions

Although no SNPs in THBS2 were associated with LSS, haplotypes (HAP4 and HAP5) were significantly associated with progression of LSS in the Korean population, whereas another haplotype (HAP1) may play a protective role against LSS development.

Agah A, Kyriakides TR, Bornstein P (2005) Proteolysis of cell-surface tissue transglutaminase by matrix metalloproteinase-2 contributes to the adhesive defect and matrix abnormalities in thrombospondin-2-null fibroblasts and mice. Am J Pathol 167:81–88PubMedCrossRef

Ala-Kokko L (2002) Genetic risk factors for lumbar disc disease. Ann Med 34:42–47PubMedCrossRef

Armstrong LC, Bornstein P (2003) Thrombospondins 1 and 2 function as inhibitors of angiogenesis. Matrix Biol 22:63–71PubMedCrossRef

Ashokkumar M, Anbarasan C, Saibabu R, Kuram S, Raman SC, Cherian KM (2011) An association study of thrombospondin 1 and 2 SNPs with coronary artery disease and myocardial infarction among South Indians. Thromb Res 128:e49–e53PubMedCrossRef

Bein K, Simons M (2000) Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity. J Biol Chem 275:32167–32173PubMedCrossRef

Bornstein P (1992) Thrombospondins: structure and regulation of expression. FASEB J 6:3290–3299PubMed

Bornstein P (2001) Thrombospondins as matricellular modulators of cell function. J Clin Invest 107:929–934PubMedCentralPubMedCrossRef

Bornstein P (2009) Thrombospondins function as regulators of angiogenesis. J Cell Commun Signal 3:189–200PubMedCentralPubMedCrossRef

Bornstein P, Agah A, Kyriakides TR (2004) The role of thrombospondins 1 and 2 in the regulation of cell-matrix interactions, collagen fibril formation, and the response to injury. Int J Biochem Cell Biol 36:1115–1125PubMedCrossRef

10.

Bornstein P, Sage EH (1994) Thrombospondins. Methods Enzymol 245:62–85PubMed

11.

Cursiefen C, Maruyama K, Bock F, Saban D, Sadrai Z, Lawler J, Dana R, Masli S (2011) Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med 208:1083–1092PubMedCentralPubMedCrossRef

12.

Excoffier L, Slatkin M (1995) Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol Biol Evol 12:921–927PubMed

13.

Gruber HE, Ingram JA, Hanley EN Jr (2006) Immunolocalization of thrombospondin in the human and sand rat intervertebral disc. Spine (Phila Pa 1976) 31:2556–2561CrossRef

14.

Hahn-Dantona E, Ruiz JF, Bornstein P, Strickland DK (2001) The low density lipoprotein receptor-related protein modulates levels of matrix metalloproteinase 9 (MMP-9) by mediating its cellular catabolism. J Biol Chem 276:15498–15503PubMedCrossRef

15.

Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S (2008) A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet 82:1122–1129PubMedCentralPubMedCrossRef

16.

Hyun SJ, Park BG, Rhim SC, Bae CW, Lee JK, Roh SW, Jeon SR (2011) A haplotype at the COL9A2 gene locus contributes to the genetic risk for lumbar spinal stenosis in the Korean population. Spine (Phila Pa 1976) 36:1273–1278CrossRef

17.

Koga H, Sakou T, Taketomi E, Hayashi K, Numasawa T, Harata S, Yone K, Matsunaga S, Otterud B, Inoue I, Leppert M (1998) Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet 62:1460–1467PubMedCentralPubMedCrossRef

18.

Kyriakides TR, Zhu YH, Smith LT, Bain SD, Yang Z, Lin MT, Danielson KG, Iozzo RV, LaMarca M, McKinney CE, Ginns EI, Bornstein P (1998) Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. J Cell Biol 140:419–430PubMedCrossRef

19.

Maeda S, Ishidou Y, Koga H, Taketomi E, Ikari K, Komiya S, Takeda J, Sakou T, Inoue I (2001) Functional impact of human collagen alpha2(XI) gene polymorphism in pathogenesis of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res 16:948–957PubMedCrossRef

20.

Nakao T, Kurita N, Komatsu M, Yoshikawa K, Iwata T, Utsunomiya T, Shimada M (2011) Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer. Int J Clin Oncol 16:145–152PubMedCrossRef

21.

Noponen-Hietala N, Kyllonen E, Mannikko M, Ilkko E, Karppinen J, Ott J, Ala-Kokko L (2003) Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis. Ann Rheum Dis 62:1208–1214PubMedCrossRef

22.

Punekar S, Zak S, Kalter VG, Dobransky L, Punekar I, Lawler JW, Gutierrez LS (2008) Thrombospondin 1 and its mimetic peptide ABT-510 decrease angiogenesis and inflammation in a murine model of inflammatory bowel disease. Pathobiology 75:9–21PubMedCrossRef

23.

Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M, Kubo T, Toyama Y, Kimura T, Nakamura Y, Ikegawa S (2005) A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet 37:607–612PubMedCrossRef

24.

Sheehan JM, Shaffrey CI, Jane JA Sr (2001) Degenerative lumbar stenosis: the neurosurgical perspective. Clin Orthop Relat Res 384:61–74PubMedCrossRef

25.

Sirvanci M, Bhatia M, Ganiyusufoglu KA, Duran C, Tezer M, Ozturk C, Aydogan M, Hamzaoglu A (2008) Degenerative lumbar spinal stenosis: correlation with Oswestry disability index and MR imaging. Eur Spine J 17:679–685PubMedCentralPubMedCrossRef

26.

Spivak JM (1998) Degenerative lumbar spinal stenosis. J Bone Jt Surg Am 80:1053–1066

27.

Vallejo AN, Mugge LO, Klimiuk PA, Weyand CM, Goronzy JJ (2000) Central role of thrombospondin-1 in the activation and clonal expansion of inflammatory T cells. J Immunol 164:2947–2954PubMed

28.

Vallejo AN, Yang H, Klimiuk PA, Weyand CM, Goronzy JJ (2003) Synoviocyte-mediated expansion of inflammatory T cells in rheumatoid synovitis is dependent on CD47-thrombospondin 1 interaction. J Immunol 171:1732–1740PubMed

29.

Wynne-Davies R, Walsh WK, Gormley J (1981) Achondroplasia and hypochondroplasia. Clinical variation and spinal stenosis. J Bone Jt Surg Br 63B:508–515

30.

Yang Z, Kyriakides TR, Bornstein P (2000) Matricellular proteins as modulators of cell-matrix interactions: adhesive defect in thrombospondin 2-null fibroblasts is a consequence of increased levels of matrix metalloproteinase-2. Mol Biol Cell 11:3353–3364PubMedCentralPubMedCrossRef

31.

Yang Z, Strickland DK, Bornstein P (2001) Extracellular matrix metalloproteinase 2 levels are regulated by the low density lipoprotein-related scavenger receptor and thrombospondin 2. J Biol Chem 276:8403–8408PubMedCrossRef

Title: Progression of lumbar spinal stenosis is influenced by polymorphism of thrombospondin 2 gene in the Korean population
Authors: Seung-Jae Hyun
Borae G. Park
Seung-Chul Rhim
Jun-Won Jang
Sang-Ryong Jeon
Sung-Woo Roh
Publication date: 01-01-2014
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 1/2014
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-013-2866-6

At a glance: The STEP trials

Springer Medicine

Progression of lumbar spinal stenosis is influenced by polymorphism of thrombospondin 2 gene in the Korean population

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

Surgical treatment of Scheuermann’s kyphosis using a combined antero-posterior strategy and pedicle screw constructs: efficacy, radiographic and clinical outcomes in 111 cases

Improvement in low back pain following spinal decompression: observational study of 119 patients

Synovial sarcoma of the spine: a case involving paraspinal muscle with extensive calcification and the surgical consideration in treatment

Total spondylectomy for solitary bone plasmacytoma of the lumbar spine in a young woman: a case report and review of literature

The Michel Benoist and Robert Mulholland Yearly European Spine Journal Review: a survey of the “surgical and research” articles in the European Spine Journal, 2013

The relevance of sacral and sacro-pelvic morphology in developmental lumbosacral spondylolisthesis: are they equally important?