Open Access, Peer-reviewed
pISSN 2093-4378
eISSN 2093-4386
    J Korean Soc Spine Surg. 2012 Mar;19(1):1-7. Korean.
    Published online Mar 31, 2012.
    https://doi.org/10.4184/jkss.2012.19.1.1
    © Copyright 2012 Korean Society of Spine Surgery
    Original Article

    Association of Estrogen Receptor 2(ESR 2) Gene Polymorphisms with Ossification of the Posterior Longitudinal Ligament of the Spine

    Ki Tack Kim, M.D., Sang Hun Lee, M.D., Yoon Ho Kwack, M.D.,* Eon Seok Son, M.D.,† Kyoung Jun Park, M.D. and Duk Hyun Kim, M.D.
      • Department of Orthopedic Surgery, Kyung Hee University, Kangdong Hospital, Seoul, Korea.
      • *Department of Orthopedic Surgery, Bumin Hospital, Seoul, Korea.
      • †Department of medicine, Graduate School, Kyung Hee University, Seoul, Korea.
    • Corresponding author: Yoon-Ho Kwack, M.D. Department of Orthopedic Surgery, Bumin Hospital, 657 Deungchon 3-dong, Gangseo-gu, Seoul, 157-930, Korea. TEL: 82-2-2620-0003, FAX: 82-2-2620-0130, Email: kh21635@hanmail.net
    Received August 01, 2011; Revised December 01, 2011; Accepted December 21, 2011.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Study Design

    Genetic screening of the estrogen receptor 2 (ESR2) genes in patients with ossification of the posterior longitudinal ligament (OPLL).

    Objective

    We studied the relationships between ESR2 gene polymorphisms and OPLL to understand the pathophysiology of OPLL.

    Summary of Literature Review

    The OPLL has a strong genetic component. Several familial surveys and human leukocyte antigen (HLA) haplotype studies reveal that genetic background is an important component in the occurrence of OPLL and a large number of gene analysis studies were utilized to clarify the susceptible gene for OPLL, including COL11A2, BMP-2, TNF-α, NPPS, leptin receptor, transforming growth factor (TGF)-β, Retinoic X receptor, ER, IL-1, PTH, and VDR have been performed.

    Materials and Method

    Genomic deoxyribonucleic acid (DNA) samples obtained from 164 patients (93 men and 71 women) with OPLL and 219 control subjects, without the disease (105 men and 114 women) were amplified by polymerase chain reaction, and polymorphism genotypes were determined by the restriction endonuclease digestion. The distribution of genotypes was compared between the patients with the disease and the control subjects.

    Results

    The polymorphism of ESR2 [rs1256049, exon6, Val328Val, p=0.018, odd ratio (OR)=2.41, 95 confidence interval (CI)=1.15-5.02 in the recessive model] only showed statistically significant association between the control and the OPLL groups. The rest SNPs of ESR2 did not show any significant differences between the control and the OPLL groups.

    Conclusions

    Estrogen receptor 2 (ESR2) gene polymorphisms (rs 1256049) was associated with OPLL. In future studies, we will perform target SNP chip between OPLL and candidate gene.

    Keywords
    Spine; Ossification of the posterior longitudinal ligament (OPLL); Estrogen receptor 2 (ESR 2) gene

    Figures

    Fig. 1
    Summary, genomic regions, transcripts, and products of ESR 2 gene

    Fig. 2
    (A) location of ESR 2 gene (B) comparison between ESR 1 and ESR 2 gene

    Tables

    Table 1
    Characteristics of Study Subjects (ESR2)

    Table 2
    Case-Control Association Study of ESR 2 gene in Patients with OPLL

    References

      1. Ono K, Yonenobu K, Miyamoto S, Okada K. Pathology of ossification of the posterior longitudinal ligament and ligamentum flavum. Clin Orthop Relat Res 1999;359:18–26.
      1. Taketomi E, Sakou T, Matsunaga S, Yamaguchi M. Family study of a twin with ossification of the posterior longitudinal ligament in the cervical spine. Spine (Phila Pa 1976) 1992;17 3 Suppl:S55–S56.
      1. Okamoto K, Kobashi G, Washio M, et al. Dietary habits and risk of ossification of the posterior longitudinal ligaments of the spine (OPLL); findings from a case-control study in Japan. J Bone Miner Metab 2004;22:612–617.
      1. Sakou T, Matsunaga S, Koga H. Recent progress in the study of pathogenesis of ossification of the posterior longitudinal ligament. J Orthop Sci 2000;5:310–315.
      1. Inamasu J, Guiot BH, Sachs DC. Ossification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history. Neurosurgery 2006;58:1027–1039.
      1. Hamanishi C, Tan A, Yamane T, Tomihara M, Fukuda K, Tanaka S. Ossification of the posterior longitudinal ligament. Autosomal recessive trait. Spine (Phila Pa 1976) 1995;20:205–207.
      1. Koga H, Hayashi K, Taketomi E, et al. Restriction fragment length polymorphism of genes of the alpha 2(XI) collagen, bone morphogenetic protein-2, alkaline phosphatase, and tumor necrosis factor-alpha among patients with ossification of posterior longitudinal ligament and controls from the Japanese population. Spine (Phila Pa 1976) 1996;21:469–473.
      1. Inoue I, Ikeda R, Tsukahara S. Current topics in pharmacological research on bone metabolism: Promyelotic leukemia zinc finger (PLZF) and tumor necrosis factor-alpha-stimulated gene 6 (TSG-6) identified by gene expression analysis play roles in the pathogenesis of ossification of the posterior longitudinal ligament. J Pharmacol Sci 2006;100:205–210.
      1. Tahara M, Aiba A, Yamazaki M, et al. The extent of ossification of posterior longitudinal ligament of the spine associated with nucleotide pyrophosphatase gene and leptin receptor gene polymorphisms. Spine (Phila Pa 1976) 2005;30:877–880.
      1. Inamasu J, Guiot BH, Sachs DC. Ossification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history. Neurosurgery 2006;58:1027–1039.
      1. Terayama K. Genetic studies on ossification of the posterior longitudinal ligament of the spine. Spine (Phila Pa 1976) 1989;14:1184–1191.
      1. Geng L, Yao Z, Yang H, Luo J, Han L, Lu Q. Association of CA repeat polymorphism in estrogen receptor beta gene with postmenopausal osteoporosis in Chinese. J Genet Genomics 2007;34:868–876.
      1. Khosla S, Riggs BL, Atkinson EJ, et al. Relationship of estrogen receptor genotypes to bone mineral density and to rates of bone loss in men. J Clin Endocrinol Metab 2004;89:1808–1816.
      1. Lau HH, Ho AY, Luk KD, Kung AW. Estrogen receptor beta gene polymorphisms are associated with higher bone mineral density in premenopausal, but not postmenopausal southern Chinese women. Bone 2002;31:276–281.
      1. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 1995;80:3689–3698.
      1. Gennari L, Merlotti D, De Paola V, et al. Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol 2005;161:307–320.
      1. Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994;331:1056–1061.
      1. 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.
      1. Wang PN, Chen SS, Liu HC, Fuh JL, Kuo BI, Wang SJ. Ossification of the posterior longitudinal ligament of the spine. A case-control risk factor study. Spine (Phila Pa 1976) 1999;24:142–144.
      1. Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 1996;392:49–53.
      1. Bord S, Horner A, Beavan S, Compston J. Estrogen receptors alpha and beta are differentially expressed in developing human bone. J Clin Endocrinol Metab 2001;86:2309–2314.
      1. Sims NA, Clément-Lacroix P, Minet D, et al. A functional androgen receptor is not sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor-deficient mice. J Clin Invest 2003;111:1319–1327.
      1. Spelsberg TC, Subramaniam M, Riggs BL, Khosla S. The actions and interactions of sex steroids and growth factors/cytokines on the skeleton. Mol Endocrinol 1999;13:819–828.
      1. Pensler JM, Radosevich JA, Higbee R, Langman CB. Osteoclasts isolated from membranous bone in children exhibit nuclear estrogen and progesterone receptors. J Bone Miner Res 1990;5:797–802.
      1. Lurie G, Wilkens LR, Thompson PJ, et al. Genetic polymorphisms in the estrogen receptor beta (ESR2) gene and the risk of epithelial ovarian carcinoma. Cancer Causes Control 2009;20:47–55.
      1. Ashworth JJ, Smyth JV, Pendleton N, et al. Polymorphisms spanning the 0N exon and promoter of the estrogen receptor-beta (ERbeta) gene ESR2 are associated with venous ulceration. Clin Genet 2008;73:55–61.
      1. Rexrode KM, Ridker PM, Hegener HH, Buring JE, Manson JE, Zee RY. Polymorphisms and haplotypes of the estrogen receptor-beta gene (ESR2) and cardiovascular disease in men and women. Clin Chem 2007;53:1749–1756.
      1. Maruyama A, Nakayama T, Sato N, Mizutani Y, Furuya K, Yamamoto T. Association study using single nucleotide polymorphisms in the estrogen receptor beta (ESR2) gene for preeclampsia. Hypertens Res 2004;27:903–909.
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    MeSH Terms
    DNA
    DNA Restriction Enzymes
    Digestion
    Estrogen Receptor beta
    Estrogens
    Genetic Testing
    Genotype
    Haplotypes
    Humans
    Interleukin-1
    Leukocytes
    Longitudinal Ligaments
    Male
    Ossification of Posterior Longitudinal Ligament
    Polymerase Chain Reaction
    Polymorphism, Single Nucleotide
    Receptors, Leptin
    Spine
    Succinimides
    Transforming Growth Factors
    Tumor Necrosis Factor-alpha
    Metrics
    Share
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