J Bone Metab.  2014 May;21(2):127-132. 10.11005/jbm.2014.21.2.127.

Genetics of Ossification of the Posterior Longitudinal Ligament of the Spine: A Mini Review

• Ikegawa S

• KMID: 2241533
• DOI: http://doi.org/10.11005/jbm.2014.21.2.127

Abstract

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common disease in aging populations and sometimes results in serious neurological problems due to compression of the spinal cord and nerve roots. OPLL is a multi-factorial (polygenic) disease controlled by genetic and environmental factors. Studies searching for the genetic component of OPLL, using linkage and association analyses, are in progress and several susceptibility genes have been reported. This paper reviews the recent progress in the genetic study of OPLL and comments on its future task.

Keyword

Genetic association studies; Ossification of posterior longitudinal ligament; Polymorphism

MeSH Terms

Aging
Genetic Association Studies
Genetics*
Longitudinal Ligaments*
Ossification of Posterior Longitudinal Ligament
Spinal Cord
Spine*

Reference

1. Matsunaga S, Sakou T. Overview of epidemiology and genetics. In : Yonenobu K, Nakamura K, Toyama Y, editors. Ossification of the posterior longitudinal ligament. 2nd ed. Tokyo: Springer;2006. p. 7–9.

2. Matsunaga S, Sakou T. Ossification of the posterior longitudinal ligament of the cervical spine: etiology and natural history. Spine (Phila Pa 1976). 2012; 37:E309–E314.

3. Saetia K, Cho D, Lee S, et al. Ossification of the posterior longitudinal ligament: a review. Neurosurg Focus. 2011; 30:E1.

4. Ohtsuka K, Terayama K, Yanagihara M, et al. A radiological population study on the ossification of the posterior longitudinal ligament in the spine. Arch Orthop Trauma Surg. 1987; 106:89–93.

5. Okawa A, Nakamura I, Goto S, et al. Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat Genet. 1998; 19:271–273.

6. Okazaki T, Takuwa Y, Yamamoto M, et al. Ossification of the paravertebral ligaments: a frequent complication of hypoparathyroidism. Metabolism. 1984; 33:710–713.

7. Taguchi T. Etiology and pathogenesis. In : Yonenobu K, Nakamura K, Toyama Y, editors. Ossification of the posterior longitudinal ligament. 2nd ed. Tokyo: Springer;2006. p. 33–35.

8. Wu JC, Liu L, Chen YC, et al. Ossification of the posterior longitudinal ligament in the cervical spine: an 11-year comprehensive national epidemiology study. Neurosurg Focus. 2011; 30:E5.

9. Kobashi G, Washio M, Okamoto K, et al. High body mass index after age 20 and diabetes mellitus are independent risk factors for ossification of the posterior longitudinal ligament of the spine in Japanese subjects: a case-control study in multiple hospitals. Spine (Phila Pa 1976). 2004; 29:1006–1010.

10. Shingyouchi Y, Nagahama A, Niida M. Ligamentous ossification of the cervical spine in the late middle-aged Japanese men. Its relation to body mass index and glucose metabolism. Spine (Phila Pa 1976). 1996; 21:2474–2478.

11. Terayama K. Genetic studies on ossification of the posterior longitudinal ligament of the spine. Spine (Phila Pa 1976). 1989; 14:1184–1191.

12. Matsunaga S, Yamaguchi M, Hayashi K, et al. Genetic analysis of ossification of the posterior longitudinal ligament. Spine (Phila Pa 1976). 1999; 24:937–939.

13. Koga H, Sakou T, Taketomi E, et al. Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 1998; 62:1460–1467.

14. Numasawa T, Koga H, Ueyama K, et al. Human retinoic X receptor beta: complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine. J Bone Miner Res. 1999; 14:500–508.

15. Tanaka T, Ikari K, Furushima K, et al. Genomewide linkage and linkage disequilibrium analyses identify COL6A1, on chromosome 21, as the locus for ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet. 2003; 73:812–822.

16. Furushima K, Shimo-Onoda K, Maeda S, et al. Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res. 2002; 17:128–137.

17. Karasugi T, Nakajima M, Ikari K, et al. A genome-wide sib-pair linkage analysis of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Metab. 2013; 31:136–143.

18. Nakamura I, Ikegawa S, Okawa A, et al. Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL). Hum Genet. 1999; 104:492–497.

19. Kamiya M, Harada A, Mizuno M, et al. Association between a polymorphism of the transforming growth factor-beta1 gene and genetic susceptibility to ossification of the posterior longitudinal ligament in Japanese patients. Spine (Phila Pa 1976). 2001; 26:1264–1267.

20. Ogata N, Koshizuka Y, Miura T, et al. Association of bone metabolism regulatory factor gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity. Spine (Phila Pa 1976). 2002; 27:1765–1771.

21. Kobashi G, Ohta K, Washio M, et al. FokI variant of vitamin D receptor gene and factors related to atherosclerosis associated with ossification of the posterior longitudinal ligament of the spine: a multi-hospital case-control study. Spine (Phila Pa 1976). 2008; 33:E553–E558.

22. Wang H, Liu D, Yang Z, 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. 2008; 17:956–964.

23. Liu Y, Zhao Y, Chen Y, et al. RUNX2 polymorphisms associated with OPLL and OLF in the Han population. Clin Orthop Relat Res. 2010; 468:3333–3341.

24. Chung WS, Nam DH, Jo DJ, et al. Association of toll-like receptor 5 gene polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine in korean population. J Korean Neurosurg Soc. 2011; 49:8–12.

25. Kim DH, Jeong YS, Chon J, et al. Association between interleukin 15 receptor, alpha (IL15RA) polymorphism and Korean patients with ossification of the posterior longitudinal ligament. Cytokine. 2011; 55:343–346.

26. Ren Y, Liu ZZ, Feng J, et al. Association of a BMP9 haplotype with ossification of the posterior longitudinal ligament (OPLL) in a Chinese population. PLoS One. 2012; 7:e40587.

27. Horikoshi T, Maeda K, Kawaguchi Y, et al. A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine. Hum Genet. 2006; 119:611–616.

28. Nakajima M, Takahashi A, Kou I, et al. New sequence variants in HLA class II/III region associated with susceptibility to knee osteoarthritis identified by genome-wide association study. PLoS One. 2010; 5:e9723.

29. Kou I, Takahashi A, Urano T, et al. Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese. PLoS One. 2011; 6:e19641.

30. Takahashi Y, Kou I, Takahashi A, et al. A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis. Nat Genet. 2011; 43:1237–1240.

31. Song YQ, Karasugi T, Cheung KM, et al. Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. J Clin Invest. 2013; 123:4909–4917.

32. Miyamoto Y, Mabuchi A, Shi D, et al. A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet. 2007; 39:529–533.

33. Hwang JY, Lee SH, Go MJ, et al. Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture. J Med Genet. 2013; 50:212–219.

34. Wei JC, Hsu YW, Hung KS, et al. Association study of polymorphisms rs4552569 and rs17095830 and the risk of ankylosing spondylitis in a Taiwanese population. PLoS One. 2013; 8:e52801.

35. Kou I, Takahashi Y, Johnson TA, et al. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet. 2013; 45:676–679.