Analysis of FokI polymorphism of vitamin D receptor gene in intervertebral disc degeneration.
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ABSTRACT: Aim
We have hypothesized a possible relationship between disc degeneration (DD) and VDR FokI/T2C polymorphism.Methods
A case-control study was performed comprising 121 Brazilian patients with confirmed DD by nuclear magnetic resonance and a control group consisting of 131 healthy patients without a history of disc cysts of the lumbar spine. Detection of VDR FokI/T2C polymorphism was performed using restriction fragment length polymorphism-polymerase chain reaction. The chi-square test was used to compare allele and genotype frequencies between groups, and a p-value of <0.05 was considered statistically significant.Results
The results disclosed statistical difference between allele distribution among cases and controls (p=0.025, odds ratio=1.58, confidence interval=1.07-2.32) considering VDR FokI/T2C polymorphism.Conclusion
The results showed a positive association between VDR FokI/T2C polymorphism and DD in Brazilian patients tested.
SUBMITTER: Vieira LA
PROVIDER: S-EPMC4150369 | biostudies-literature | 2014 Sep
REPOSITORIES: biostudies-literature
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Project description:Vitamin D is known to have immunomodulatory effects, is involved in osteo-cartilaginous metabolism, and may have a role in human intervertebral disc pathophysiology. Although a link between vitamin D receptor (VDR) gene variants and disc degeneration-related pathologies has been observed, its functional contribution to pathologic processes has not been assessed yet. The aim of this study was to investigate the response of disc cells to vitamin D in terms of the regulation of proliferation, metabolism, and inflammatory processes, with a particular focus on the FokI VDR genotype. However, although it was found that vitamin D had a pro-apoptotic effect regardless of genotype, an up-regulation of IL-1Ra and downregulation of IL-6 was found to be evident only in Ff cells. Regarding the metabolic effects, in Ff cells, vitamin D promoted an upregulation of the aggrecan in inflammatory conditions but did not have an effect on the expression of collagen-related markers. Moreover, cells bearing the Ff genotype were the most responsive to vitamin D in the upregulation of catabolic markers. In addition, in contrast to the FF genotype, vitamin D downregulated the vitamin D-dependent signaling pathway in inflamed Ff cells, counteracting the inflammation-mediated catabolic effects. In conclusion, Ff cells were found to be more responsive to the anti-inflammatory and catabolic effects of vitamin D, which is likely to be related to matrix remodeling.
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Project description:Intervertebral disk degeneration (IDD) is strongly associated with genetic predisposition and environmental susceptibility. Several studies been conducted to investigate the potential association between IDD and FokI polymorphism located in the gene encoding the vitamin D receptor (VDR), and inconsistent conclusions had been reached among different ethnic populations. In order to assess the association between the FokI polymorphism and the risk of IDD, we performed a comprehensive and systematic meta-analysis. Candidate articles were retrieved from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and China Biology Medical (CBM) with strict inclusion criteria in January 2015. Among the 54 articles that were retrieved, only eight studies met the inclusion criteria. The pooled data analysis based on allele contrast, homozygote, heterozygote, dominant, and recessive models revealed no significant correlation between the FokI polymorphism and the risk of IDD. However, when stratified by ethnicity, significant associations were detected for Hispanics based on allele contrast (OR=1.395, 95% CI=1.059-1.836, P=0.018), homozygote (OR=1.849, 95% CI=1.001-3.416, P=0.049), heterozygote (OR=1.254, 95% CI=1.049-1.498, P=0.013), and dominant (OR=1.742, 95% CI=1.174-2.583, P=0.006) models, and for Asians using the dominant model (OR=1.293, 95% CI=1.025-1.632, P=0.030), whereas there is no significant association detected for Caucasians. In conclusion, FokI polymorphism is not generally associated with IDD, but there is increased risk for IDD in Hispanics and Asians carrying FokI allele T.
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Project description:BackgroundA series of studies have been conducted to evaluate the associations between vitamin D receptor (VDR) and aggrecan variable numbers of tandem repeat (VNTR) polymorphisms and the risk of intervertebral disc degeneration (IDD), but produced conflicting results.Objectivewe performed a meta-analysis to address a more accurate estimation of the associations between the above gene polymorphisms and the risk of IDD.MethodsA comprehensive literature search was conducted to identify all the relevant studies. The fixed or random effect model was selected based on the heterogeneity test among studies evaluated using the I(2). Publication bias was estimated using Begg's funnel plots and Egger's regression test.ResultsA total of 9, 5, 3, and 7 studies were finally included in the analyses for the associations between the VDR TaqI (rs731236), FokI (rs2228570), ApaI (rs7975232), or aggrecan VNTR polymorphisms and the risk of IDD, respectively. The combined results showed that none of the VDR (TaqI, FokI, ApaI) polymorphisms were significantly associated with the risk of IDD. In contrast, the alleles with shorter VNTR length was found to significantly increase the risk of IDD (≦25 vs. >25: OR = 1.850, 95%CI 1.477-2.318; ≦23 vs. >23: OR = 1.955, 95%CI 1.41-2.703). Subgroup analysis confirmed the above results. After excluding studies deviated from Hardy-Weinberg equilibrium (HWE) in controls, no other studies were found to significantly influence the pooled effects in each genetic model. No potential publication bias was detected.ConclusionThis meta-analysis suggested that the alleles with shorter VNTR length significantly increased the risk of IDD, while the VDR (TaqI, FokI, ApaI) gene polymorphisms were not significantly associated with the risk of IDD. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.
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Project description:Several studies have evaluated the association between vitamin D receptor, matrix metalloproteinase 3 (MMP-3) polymorphisms and the risk of intervertebral disc degeneration susceptibility. The findings were inconsistent. This meta-analysis aimed to systematically assess the association between vitamin D receptor, MMP-3 polymorphisms and the risk of intervertebral disc degeneration susceptibility. A search of various databases was done covering all papers published until December 31th, 2014. Eight, 4, 3 studies were finally included that addressed the risk of intervertebral disc degeneration susceptibility and vitamin D receptor FokI (rs2228570), ApaI (rs7975232), and MMP-3 (rs731236) polymorphisms, respectively. FokI (f vs. F: summary odds ratio [OR], 1.13; 95% confidence interval [CI], 0.76-1.69; ff vs. FF: OR, 1.02; 95% CI, 0.59-1.77; ff vs. Ff/FF: OR, 1.05; 95% CI, 0.70-1.58), ApaI (a vs. A: OR, 0.73; 95% CI, 0.45-1.19; aa vs. AA: OR, 0.53; 95% CI, 0.22-1.25 p=0.14; aa vs. AA/Aa: OR, 0.69; 95% CI, 0.53-0.89) in the vitamin D receptor gene and MMP3 polymorphisms (5A vs. 6A: OR, 1.92; 95% CI, 0.77-4.80; 5A5A vs. 6A6A: OR, 2.17; 95% CI, 0.75-6.24; 5A5A vs. 5A6A/6A6A: OR, 1.58; 95% CI, 0.72-3.44) were not obviously associated with risk of intervertebral disc degeneration susceptibility. FokI, ApaI polymorphisms in the vitamin D receptor gene and MMP-3 polymorphism are not obvious risk factors for intervertebral disc degeneration susceptibility.
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