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

Ki Tack Kim; Sang Hun Lee; Yoon Ho Kwack; Eon Seok Son; Kyoung Jun Park; Duk Hyun Kim

doi:10.4184/JKSS.2021.19.1.1

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Kim, Lee, Kwack, Son, Park, and Kim: Association of Estrogen Receptor 2(ESR 2) Gene Polymorphisms with Ossification of the Posterior Longitudinal Ligament of the Spine

Original Research

J Korean Soc Spine Surg 2012;19(1):1-7.

Published online: 18 March 2013

DOI: https://doi.org/10.4184/JKSS.2021.19.1.1

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., 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

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 E-mail: kh21635@hanmail.net

Received 1 August 20111 December 2011 Accepted 31 December 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

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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

Table 1.

Characteristics of Study Subjects (ESR2)

	Patients with OPLL (n=164)	Controls (n=219)
Age (years, mean ±S.D.)	60.70±10.91	59.28±14.13
Sex distribution (n, male : female)	93:71	105:114
Involved number of spines	2.43±1.38
Type of OPLL (n)
Continuous	24
Segmental	29
Mixed	22
Localized	89
Associated conditions (n)
DISH	4
OYL	32
Myelopathy	33

^† OPLL: Ossification of posterior longitudinal ligament

^† DISH: Diffuse idiopathic skeletal hyperostosis

^† OYL: Ossification yellow ligament

Table 2.

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

SNP	Genotype	Control	OPLL	Codominant	P	Dominant	P	Recessive	P
(Locus)	Genotype	n (%)	n (%)	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
rs1256049 (exon6, Val328Val)	G/G	116(50.7)	76(46.3)	1.32 (0.96-1.81)	0.085	1.20 (0.80-1.79)	0.380	2.41 (1.15-5.02)	0.018
	A/G	100(43.7)	68(41.5)
	A/A	13(5.7)	20(12.2)
rs928554 (exon9,3UTR)	A/A	100(43.7)	79(48.2)	0.87 (0.64-1.18)	0.380	0.81 (0.54-1.21)	0.300	0.92 (0.48-1.77)	0.810
	A/G	103(45)	68(41.5)
	G/G	26(11.3)	17(10.4)
rs1255998 (exon9,3UTR)	C/C	72(31.4)	46(28.1)	1.15 (0.88-1.52)	0.310	1.16 (0.75-1.81)	0.510	1.28 (0.80-2.05)	0.300
	C/G	107(46.7)	75(45.7)
	G/G	50(21.8)	43(26.2)

^† OPLL: Ossification of posterior longitudinal ligament

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