Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with ossification of the posterior longitudinal ligament of the cervical spine

Jae Joon Lim, Dong Ah Shin, Young Joo Jeon, Hemant Kumar, Seil Sohn, Hyoung Sik Min, Jang Bo Lee, Sung Uk Kuh, Keung Nyun Kim, Jung Oh Kim, Ok Joon Kim, Alexander E. Ropper, Nam Keun Kim, In BoHan

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Abstract

Background Ossification of the posterior longitudinal ligament (OPLL) of the spine is considered a multifactorial and polygenic disease. We aimed to investigate the association between four single nucleotide polymorphisms (SNPs) of pre-miRNAs [miR-146aC>G (rs2910164), miR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444)] and the risk of cervical OPLL in the Korean population. Methods The genotypic frequencies of these four SNPs were analyzed in 207 OPLL patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Findings For four SNPs in pre-miRNAs, no significant differences were found between OPLL patients and controls. However, subgroup analysis based on OPLL subgroup (continuous: continuous type plus mixed type, segmental: segmental and localized type) showed that miR-499GG genotype was associated with an increased risk of segmental type OPLL (adjusted odds ratio = 4.314 with 95% confidence interval: 1.109-16.78). In addition, some allele combinations (C-T-T-G, G-T-T-A, and G-T-C-G of miR-146a/-149/-196a2/-499) and combined genotypes (miR-149TC/miR-196a2TT) were associated with increased OPLL risk, whereas the G-T-T-G and G-C-C-G allele combinations were associated with decreased OPLL risk. Conclusion The results indicate that GG genotype of miR-499 is associated with significantly higher risks of OPLL in the segmental OPLL group. The miR-146a/-149/-196a2/-499 allele combinations may be a genetic risk factor for cervical OPLL in the Korean population.

Original languageEnglish
Article numbere0159756
JournalPloS one
Volume11
Issue number7
DOIs
Publication statusPublished - 2016 Jul

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Ossification of Posterior Longitudinal Ligament
cervical spine
Ligaments
ligaments
bone formation
Polymorphism
genetic polymorphism
Single Nucleotide Polymorphism
single nucleotide polymorphism
Alleles
Genotype
Nucleotides
MicroRNAs
alleles
genotype
Ossification of the posterior longitudinal ligament of the spine
Polymerase chain reaction
spine (bones)
Restriction Fragment Length Polymorphisms
Population

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lim, Jae Joon ; Shin, Dong Ah ; Jeon, Young Joo ; Kumar, Hemant ; Sohn, Seil ; Min, Hyoung Sik ; Lee, Jang Bo ; Kuh, Sung Uk ; Kim, Keung Nyun ; Kim, Jung Oh ; Kim, Ok Joon ; Ropper, Alexander E. ; Kim, Nam Keun ; BoHan, In. / Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with ossification of the posterior longitudinal ligament of the cervical spine. In: PloS one. 2016 ; Vol. 11, No. 7.
@article{c2e9cb9ca88340359389616bf882a852,
title = "Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with ossification of the posterior longitudinal ligament of the cervical spine",
abstract = "Background Ossification of the posterior longitudinal ligament (OPLL) of the spine is considered a multifactorial and polygenic disease. We aimed to investigate the association between four single nucleotide polymorphisms (SNPs) of pre-miRNAs [miR-146aC>G (rs2910164), miR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444)] and the risk of cervical OPLL in the Korean population. Methods The genotypic frequencies of these four SNPs were analyzed in 207 OPLL patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Findings For four SNPs in pre-miRNAs, no significant differences were found between OPLL patients and controls. However, subgroup analysis based on OPLL subgroup (continuous: continuous type plus mixed type, segmental: segmental and localized type) showed that miR-499GG genotype was associated with an increased risk of segmental type OPLL (adjusted odds ratio = 4.314 with 95{\%} confidence interval: 1.109-16.78). In addition, some allele combinations (C-T-T-G, G-T-T-A, and G-T-C-G of miR-146a/-149/-196a2/-499) and combined genotypes (miR-149TC/miR-196a2TT) were associated with increased OPLL risk, whereas the G-T-T-G and G-C-C-G allele combinations were associated with decreased OPLL risk. Conclusion The results indicate that GG genotype of miR-499 is associated with significantly higher risks of OPLL in the segmental OPLL group. The miR-146a/-149/-196a2/-499 allele combinations may be a genetic risk factor for cervical OPLL in the Korean population.",
author = "Lim, {Jae Joon} and Shin, {Dong Ah} and Jeon, {Young Joo} and Hemant Kumar and Seil Sohn and Min, {Hyoung Sik} and Lee, {Jang Bo} and Kuh, {Sung Uk} and Kim, {Keung Nyun} and Kim, {Jung Oh} and Kim, {Ok Joon} and Ropper, {Alexander E.} and Kim, {Nam Keun} and In BoHan",
year = "2016",
month = "7",
doi = "10.1371/journal.pone.0159756",
language = "English",
volume = "11",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

Lim, JJ, Shin, DA, Jeon, YJ, Kumar, H, Sohn, S, Min, HS, Lee, JB, Kuh, SU, Kim, KN, Kim, JO, Kim, OJ, Ropper, AE, Kim, NK & BoHan, I 2016, 'Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with ossification of the posterior longitudinal ligament of the cervical spine', PloS one, vol. 11, no. 7, e0159756. https://doi.org/10.1371/journal.pone.0159756

Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with ossification of the posterior longitudinal ligament of the cervical spine. / Lim, Jae Joon; Shin, Dong Ah; Jeon, Young Joo; Kumar, Hemant; Sohn, Seil; Min, Hyoung Sik; Lee, Jang Bo; Kuh, Sung Uk; Kim, Keung Nyun; Kim, Jung Oh; Kim, Ok Joon; Ropper, Alexander E.; Kim, Nam Keun; BoHan, In.

In: PloS one, Vol. 11, No. 7, e0159756, 07.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with ossification of the posterior longitudinal ligament of the cervical spine

AU - Lim, Jae Joon

AU - Shin, Dong Ah

AU - Jeon, Young Joo

AU - Kumar, Hemant

AU - Sohn, Seil

AU - Min, Hyoung Sik

AU - Lee, Jang Bo

AU - Kuh, Sung Uk

AU - Kim, Keung Nyun

AU - Kim, Jung Oh

AU - Kim, Ok Joon

AU - Ropper, Alexander E.

AU - Kim, Nam Keun

AU - BoHan, In

PY - 2016/7

Y1 - 2016/7

N2 - Background Ossification of the posterior longitudinal ligament (OPLL) of the spine is considered a multifactorial and polygenic disease. We aimed to investigate the association between four single nucleotide polymorphisms (SNPs) of pre-miRNAs [miR-146aC>G (rs2910164), miR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444)] and the risk of cervical OPLL in the Korean population. Methods The genotypic frequencies of these four SNPs were analyzed in 207 OPLL patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Findings For four SNPs in pre-miRNAs, no significant differences were found between OPLL patients and controls. However, subgroup analysis based on OPLL subgroup (continuous: continuous type plus mixed type, segmental: segmental and localized type) showed that miR-499GG genotype was associated with an increased risk of segmental type OPLL (adjusted odds ratio = 4.314 with 95% confidence interval: 1.109-16.78). In addition, some allele combinations (C-T-T-G, G-T-T-A, and G-T-C-G of miR-146a/-149/-196a2/-499) and combined genotypes (miR-149TC/miR-196a2TT) were associated with increased OPLL risk, whereas the G-T-T-G and G-C-C-G allele combinations were associated with decreased OPLL risk. Conclusion The results indicate that GG genotype of miR-499 is associated with significantly higher risks of OPLL in the segmental OPLL group. The miR-146a/-149/-196a2/-499 allele combinations may be a genetic risk factor for cervical OPLL in the Korean population.

AB - Background Ossification of the posterior longitudinal ligament (OPLL) of the spine is considered a multifactorial and polygenic disease. We aimed to investigate the association between four single nucleotide polymorphisms (SNPs) of pre-miRNAs [miR-146aC>G (rs2910164), miR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444)] and the risk of cervical OPLL in the Korean population. Methods The genotypic frequencies of these four SNPs were analyzed in 207 OPLL patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Findings For four SNPs in pre-miRNAs, no significant differences were found between OPLL patients and controls. However, subgroup analysis based on OPLL subgroup (continuous: continuous type plus mixed type, segmental: segmental and localized type) showed that miR-499GG genotype was associated with an increased risk of segmental type OPLL (adjusted odds ratio = 4.314 with 95% confidence interval: 1.109-16.78). In addition, some allele combinations (C-T-T-G, G-T-T-A, and G-T-C-G of miR-146a/-149/-196a2/-499) and combined genotypes (miR-149TC/miR-196a2TT) were associated with increased OPLL risk, whereas the G-T-T-G and G-C-C-G allele combinations were associated with decreased OPLL risk. Conclusion The results indicate that GG genotype of miR-499 is associated with significantly higher risks of OPLL in the segmental OPLL group. The miR-146a/-149/-196a2/-499 allele combinations may be a genetic risk factor for cervical OPLL in the Korean population.

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U2 - 10.1371/journal.pone.0159756

DO - 10.1371/journal.pone.0159756

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VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

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