INTERVERTEBRAL DISC DEGENERATION LINKED TO STRUCTURAL GENE VARIATIONS

2019 ◽  
Author(s):  
Saeeda Baig
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
English Language ◽  
Tandem Repeats ◽  
Lumbar Disc ◽  
Disease Process ◽  
Nucleotide Polymorphisms ◽  
Structural Protein ◽  
Lumbar Disc Degeneration

During the recent past focus has shifted from identifying intervertebral disc degeneration as being caused by physical exposure and strain to being linked with a variety of genetic variations. The objective of this review is to provide an up to date review of the existing research data regarding the relation of intervertebral disc degeneration to structural protein genes and their polymorphisms and thus help clearly establish further avenues where research into causation and treatment is needed. A comprehensive search using the keywords “Collagen”, “COL”, “Aggrecan”, “AGC”, “IVDD”, “intervertebral disc degeneration”, and “lumbar disc degeneration” from PubMed and Google Scholar, where literature in the English language was selected spanning from 1991 to 2019. There are many genes involved in the production of structural components of an intervertebral disc. The issues in production of these components involve the over-expression or under-expression of their genes, and single nucleotide polymorphisms and variable number of tandem repeats affecting their structures. These structural genes include primarily the collagen and the aggrecan genes. While genetic and environmental factors all come into play with a disease process like disc degeneration, the bulk of research now shows the significantly larger impact of hereditary over exposure. While further research is needed into some of the lesser studied genes linked to IVDD and also the racial variations in genetic makeup, the focus in the near future should be on establishment of genetic testing to identify individuals at greater risk of disease and deliberation regarding the use of gene therapy to prevent disc degeneration.

Association between Measures of Vertebral Endplate Morphology and Lumbar Intervertebral Disc Degeneration

2017 ◽  
Vol 68 (2) ◽  
pp. 210-216 ◽  
Author(s):  
Semra Duran ◽  
Mehtap Cavusoglu ◽  
Hatice Gul Hatipoglu ◽  
Deniz Sozmen Cılız ◽  
Bulent Sakman
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Lumbar Disc ◽  
Lumbar Disc Degeneration ◽  
Vertebral Endplate ◽  
Lumbar Intervertebral Disc ◽  
Sagittal Diameter ◽  
Magnetic Resonance Imaging Mri ◽  
Vertebral Endplates

Purpose The aim of this study was to evaluate the association between vertebral endplate morphology and the degree of lumbar intervertebral disc degeneration via magnetic resonance imaging (MRI). Methods In total, 150 patients who met the inclusion criteria and were 20–60 years of age were retrospectively evaluated. Patients were evaluated for the presence of intervertebral disc degeneration or herniation, and the degree of degeneration was assessed at all lumbar levels. Vertebral endplate morphology was evaluated based on the endplate sagittal diameter, endplate sagittal concave angle (ECA), and endplate sagittal concave depth (ECD) on sagittal MRI. The association between intervertebral disc degeneration or herniation and endplate morphological measurements was analysed. Results In MRI, superior endplates ( ie, inferior endplates of the superior vertebra) were concave and inferior endplates ( ie, superior endplates of the inferior vertebra) were flat at all disc levels. A decrease in ECD and an increase in ECA were detected at all lumbar levels as disc degeneration increased ( P < .05). At the L4-L5 and L5-S1 levels, a decrease in ECD and an increase in ECA were detected in the group with herniated lumbar discs ( P < .05). There was no association between lumbar disc degeneration or herniation and endplate sagittal diameter at lumbar intervertebral levels ( P > .05). At all levels, ECD of women was significantly lesser than that of men and ECA of women was significantly greater than that of men ( P < .05). Conclusions There is an association between vertebral endplate morphology and lumbar intervertebral disc degeneration. Vertebral endplates at the degenerated disc level become flat; the severity of this flattening is correlated with the degree of disc degeneration.

Genetic aspects of intervertebral disc degeneration

2015 ◽  
Vol 26 (5) ◽  
pp. 581-606 ◽  
Author(s):  
Sara Hanaei ◽  
Sina Abdollahzade ◽  
Alireza Khoshnevisan ◽  
Christopher K. Kepler ◽  
Nima Rezaei
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Genetic Factors ◽  
Wide Spectrum ◽  
Nucleotide Polymorphisms ◽  
Disc Disease ◽  
Multifactorial Diseases ◽  
Common Causes

AbstractIntervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.

scholarly journals Prevalence, Patterns, and Genetic Association Analysis of Modic Vertebral Endplate Changes

2017 ◽  
Vol 11 (4) ◽  
pp. 594-600 ◽  
Author(s):  
Rishi Mugesh Kanna ◽  
Rajasekaran Shanmuganathan ◽  
Veera Ranjani Rajagopalan ◽  
Senthil Natesan ◽  
Raveendran Muthuraja ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Genetic Association ◽  
Association Analysis ◽  
Disc Degeneration ◽  
Lumbar Disc ◽  
Nucleotide Polymorphisms ◽  
Lumbar Disc Degeneration ◽  
Vertebral Endplate ◽  
Genetic Association Analysis ◽  
Study Population

<sec><title>Study Design</title><p>A prospective genetic association study.</p></sec><sec><title>Purpose</title><p>The etiology of Modic changes (MCs) is unclear. Recently, the role of genetic factors in the etiology of MCs has been evaluated. However, studies with a larger patient subset are lacking, and candidate genes involved in other disc degeneration phenotypes have not been evaluated. We studied the prevalence of MCs and genetic association of 41 candidate genes in a large Indian cohort.</p></sec><sec><title>Overview of Literature</title><p>MCs are vertebral endplate signal changes predominantly observed in the lumbar spine. A significant association between MCs and lumbar disc degeneration and nonspecific low back pain has been described, with the etiopathogenesis implicating various mechanical, infective, and biochemical factors.</p></sec><sec><title>Methods</title><p>We studied 809 patients using 1.5-T magnetic resonance imaging to determine the prevalence, patterns, distribution, and type of lumbar MCs. Genetic association analysis of 71 single nucleotide polymorphisms (SNPs) of 41 candidate genes was performed based on the presence or absence of MCs. SNPs were genotyped using the Sequenome platform, and an association test was performed using PLINK software.</p></sec><sec><title>Results</title><p>The mean age of the study population (n=809) was 36.7±10.8 years. Based on the presence of MCs, the cohort was divided into 702 controls and 107 cases (prevalence, 13%). MCs were more commonly present in the lower (149/251, 59.4%) than in the upper (102/251, 40.6%) endplates. L4–5 endplates were the most commonly affected levels (30.7%). Type 2 MCs were the most commonly observed pattern (n=206, 82%). The rs2228570 SNP of VDR (<italic>p</italic>=0.02) and rs17099008 SNP of MMP20 (<italic>p</italic>=0.03) were significantly associated with MCs.</p></sec><sec><title>Conclusions</title><p>Genetic polymorphisms of SNPs of VDR and MMP20 were significantly associated with MCs. Understanding the etiopathogenetic mechanisms of MCs is important for planning preventive and therapeutic strategies.</p></sec>

Association Between the Aggrecan Gene Variable Number of Tandem Repeats Polymorphism and Intervertebral Disc Degeneration

Spine ◽  
2007 ◽  
Vol 32 (16) ◽  
pp. 1700-1705 ◽  
Author(s):  
Svetlana Solovieva ◽  
Noora Noponen ◽  
Minna Männikkö ◽  
Päivi Leino-Arjas ◽  
Katariina Luoma ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Tandem Repeats ◽  
Variable Number

Effect of hyperglycemia on apoptosis of notochordal cells and intervertebral disc degeneration in diabetic rats

2009 ◽  
Vol 11 (6) ◽  
pp. 741-748 ◽  
Author(s):  
Ho-Yeon Won ◽  
Jong-Beom Park ◽  
Eun-Young Park ◽  
K. Daniel Riew
Keyword(s):  
Diabetes Mellitus ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Lumbar Disc ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Etiologic Factor ◽  
Notochordal Cells ◽  
Oletf Rats ◽  
Apoptosis Index

Object Diabetes mellitus is thought to be an important etiologic factor in intervertebral disc degeneration. It is known that notochordal cells gradually disappear from the nucleus pulposus (NP) of the intervertebral disc with age by undergoing apoptosis. What is not known is whether diabetes has an effect on apoptotic rates of notochordal cells. The purpose of this study was to investigate the effect of hyperglycemia on apoptosis of notochordal cells and intervertebral disc degeneration in age-matched OLETF (diabetic) and LETO (control) rats. Methods Lumbar disc tissue (L1–2 through L5–6), including cranial and caudal cartilaginous endplates, was obtained from 6- and 12-month-old OLETF and LETO rats (40 rats, 10 in each of the 4 groups). The authors examined the NP using TUNEL, histological analysis, and Western blot for expression of matrix metalloproteinase (MMP)–1, -2, -3, and -13, tissue inhibitor of metalloproteinase (TIMP)–1 and -2, and Fas (apoptosis-related protein). The apoptosis index of notochordal cells was calculated. The degree of transition of notochordal NP to fibrocartilaginous NP was classified on a scale ranging from Grade 0 (no transition) to Grade 4 (transition > 75%). The degree of expression of MMP-1, -2, -3, and -13, TIMP-1 and -2, and Fas was evaluated by densitometry. Results At 6 and 12 months of age, OLETF rats showed increased body weight and abnormal 2-hour glucose tolerance tests compared with LETO rats. The apoptosis index of notochordal cells was significantly higher in the OLETF rats than in the LETO rats at both 6 and 12 months of age. The degree of transition of notochordal NP to fibrocartilaginous NP was significantly higher in the OLETF rats than in the LETO rats at 6 and 12 months of age. The expression of MMP-1, -2, -3, and -13, TIMP-1, and Fas was higher in the OLETF rats at 6 and 12 months of age. The expression of TIMP-2 was significantly higher in the OLETF rats than in the LETO rats at 6 months of age, but not at 12. Conclusions The findings suggest that diabetes is associated with premature, excessive apoptosis of NP notochordal cells. This results in an accelerated transition of a notochordal NP to a fibrocartilaginous NP, which leads to early intervertebral disc degeneration. It remains to be determined if these premature changes are due to hyperglycemia or some other factors associated with diabetes. Understanding the mechanism by which diabetes affects disc degeneration is the first step in designing therapeutic modalities to delay or prevent disc degeneration caused by diabetes mellitus.

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