Association of VKORC1-1639G&gt;A polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine: a Korean study

Chin, Dong Kyu; Han, Inbo; Ropper, Alexander E.; Jeon, Young‐Joo; Kim, Do-Hyung; Kim, Young-Sung; Park, Youngseok; Teng, Yang D.; Kuh, Sung Uk

doi:10.1007/s00701-013-1747-4

Cited by 14 publications

(16 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Beside non-genetic factors like mechanical stress, nutrition, glucose intolerance, and high body mass index, recent studies showed numerous genes are associated with the disease. Most of these genes are vital to the ossification process like NPPS, COL11A2, COL6A1, BMP2, BMP4, TGF-β1, TGF-β3 4 5 6 7 22 24 , and often aberrant expression of these genes can cause the pathological heterogeneous ossification 25 26 . This means a certain disorder in the upstream regulatory network of these critical factors may exists during the pathological process of OPLL.…”

Section: Discussionmentioning

confidence: 99%

“…The ossified ligaments formed osteophytes that gradually increases in size, which in turns causes compression of spinal cord and may lead to neurologic symptoms or severe neurologic deficit. Recent studies have shown that single nucleotide polymorphisms (SNPs) and gene expression variations in various genes are associated with OPLL development 3 4 5 6 7 , which implies genetic factors may play key roles in this process. However, the exact pathogenesis of OPLL still remains unclear, not to mention the underlying mechanism and its regulatory network.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Chen

Zhang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Ossification of the posterior longitudinal ligament (OPLL) is a genetic disorder which involves pathological heterotopic ossification of the spinal ligaments. Although studies have identified several genes that correlated with OPLL, the underlying regulation network is far from clear. Through small RNA sequencing, we compared the microRNA expressions of primary posterior longitudinal ligament cells form OPLL patients with normal patients (PLL) and identified 218 dysregulated miRNAs (FDR < 0.01). Furthermore, assessing the miRNA profiling data of multiple cell types, we found these dysregulated miRNAs were mostly OPLL specific. In order to decipher the regulation network of these OPLL specific miRNAs, we integrated mRNA expression profiling data with miRNA sequencing data. Through computational approaches, we showed the pivotal roles of these OPLL specific miRNAs in heterotopic ossification of longitudinal ligament by discovering highly correlated miRNA/mRNA pairs that associated with skeletal system development, collagen fibril organization, and extracellular matrix organization. The results of which provide strong evidence that the miRNA regulatory networks we established may indeed play vital roles in OPLL onset and progression. To date, this is the first systematic analysis of the micronome in OPLL, and thus may provide valuable resources in finding novel treatment and diagnostic targets of OPLL.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Chen

Zhang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…There are many genes reported to be associated with OPLL in human, including ENPP1 [24, 29], collagen 6A1 [27], transforming growth factor-β (TGFB) -1 [20], TGFB-3 [30], collagen 11A2 [22], bone morphogenetic protein (BMP)-2 [46], RUNX2 [26], Fibroblast Growth factor 2 [19], BMP-9 [34], TGFB receptor type 2 [17], vitamin K epoxide reductase complex subunit 1 [8], however, the pathogenesis of OPLL remains to be elucidated. The expression analysis of OPLL related genes in Enpp1 mutant mice might be contributory to understanding the pathogenesis of OPLL.…”

Section: Discussionmentioning

confidence: 99%

A New Enpp1 allele, Enpp1ttw-Ham, Identified in an ICR Closed Colony

2014

View full text Add to dashboard Cite

We recently have reported on a novel ankylosis gene that is closely linked to the Enpp1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) gene on chromosome 10. Here, we have discovered novel mutant mice in a Jcl:ICR closed colony with ankylosis in the toes of the forelimbs at about 3 weeks of age. The mutant mice exhibited rigidity in almost all joints, including the vertebral column, which increased with age. These mice also showed hypogrowth with age after 16 weeks due to a loss of visceral fat, which may have been caused by poor nutrition. Histological examination and soft X-ray imaging demonstrated the ectopic ossification of various joints in the mutant mice. In particular, increased calcium deposits were observed in the joints of the toes, the carpal bones and the vertebral column. We sequenced all exons and exon/intron boundaries of Enpp1 in the normal and mutant mice, and identified a G-to-T substitution (c.259+1G>T) in the 5′ splice donor site of intron 2 in the Enpp1 gene of the mutant mice. This substitution led to the skipping of exon 2 (73 bp), which generated a stop codon at position 354 bp (amino acid 62) of the cDNA (p.V63Xfs). Nucleotide pyrophosphohydrolase (NPPH) activity of ENPP1 in the mutant mice was also decreased, suggesting that Enpp1 gene function is disrupted in this novel mutant. The mutant mice reported in this study will be a valuable animal model for future studies of human osteochondral diseases and malnutrition.

show abstract

“…The VKORC1 gene was investigated in 98 OPLL patients and 200 control subjects, with the −1639G> A polymorphism having a significant effect in female patients (OR 5.22, p = 0.004), but not when both sexes were considered together (p > 0.05) [52].…”

Section: Spinal Pathologymentioning

confidence: 99%

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies

Pope

Davies

Mowforth

et al. 2020

JCM

View full text Add to dashboard Cite

Degenerative cervical myelopathy (DCM) is estimated to be the most common cause of adult spinal cord impairment. Evidence that is suggestive of a genetic basis to DCM has been increasing over the last decade. A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and HuGENet databases from their origin up to 14th December 2019 to evaluate the role of single genes in DCM in its onset, clinical phenotype, and response to surgical intervention. The initial search yielded 914 articles, with 39 articles being identified as eligible after screening. We distinguish between those contributing to spinal column deterioration and those contributing to spinal cord deterioration in assessing the evidence of genetic contributions to DCM. Evidence regarding a total of 28 candidate genes was identified. Of these, 22 were found to have an effect on the radiological onset of spinal column disease, while 12 genes had an effect on clinical onset of spinal cord disease. Polymorphisms of eight genes were found to have an effect on the radiological severity of DCM, while three genes had an effect on clinical severity. Polymorphisms of six genes were found to have an effect on clinical response to surgery in spinal cord disease. There are clear genetic effects on the development of spinal pathology, the central nervous system (CNS) response to bony pathology, the severity of both bony and cord pathology, and the subsequent response to surgical intervention. Work to disentangle the mechanisms by which the genes that are reviewed here exert their effects, as well as improved quality of evidence across diverse populations is required for further investigating the genetic contribution to DCM.

show abstract

Association of VKORC1-1639G>A polymorphism with susceptibility to ossification of the posterior longitudinal ligament of the spine: a Korean study

Cited by 14 publications

References 36 publications

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

A New <i>Enpp1</i> allele, <i>Enpp1</i><i><sup>ttw-Ham</sup></i>, Identified in an ICR Closed Colony

Genetics of Degenerative Cervical Myelopathy: A Systematic Review and Meta-Analysis of Candidate Gene Studies

Contact Info

Product

Resources

About