Association of <i>VDR</i> Polymorphisms (<i>FokI</i>, <i>ApaI</i>, and <i>TaqI</i>) with Susceptibility to Lumbar Disc Herniation: Systematic Review, Meta-Analysis, Trial Sequential Analysis, and Transcriptional Prediction
<i>Background and Objectives</i>: Lumbar disc herniation (LDH) is influenced by genetic, mechanical, and behavioral factors, with genetic predisposition playing a key role. <i>Vitamin D receptor</i> (<i>VDR</i>) polymorphisms have been implicated in LDH susceptibi...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Medicina |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1648-9144/61/5/882 |
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| Summary: | <i>Background and Objectives</i>: Lumbar disc herniation (LDH) is influenced by genetic, mechanical, and behavioral factors, with genetic predisposition playing a key role. <i>Vitamin D receptor</i> (<i>VDR</i>) polymorphisms have been implicated in LDH susceptibility, warranting further investigation. This study aimed to assess the association between <i>VDR</i> polymorphisms (<i>FokI</i>, <i>ApaI</i>, and <i>TaqI</i>) and LDH risk through a systematic review, meta-analysis, and trial sequential analysis (TSA). <i>Materials and Methods</i>: A systematic literature search was conducted across PubMed, Web of Science, Scopus, Cochrane Library, and CNKI, up until 30 January 2025. A meta-analysis was performed using Review Manager 5.3, with odds ratios (ORs) and 95% confidence intervals (CIs), and heterogeneity assessed via the I<sup>2</sup> statistic. The publication bias and TSA were evaluated using CMA 3.0 and TSA software to ensure the reliability of the results. The FATHMM-XF method was applied to predict the functional effect of coding and non-coding polymorphisms. <i>Results</i>: From 79 records, 10 studies were entered into the meta-analysis. The meta-analysis results showed no significant association of <i>FokI</i> and <i>ApaI</i> polymorphisms with LDH, while <i>TaqI</i> exhibited a protective effect, particularly in Asian populations and larger studies. The subgroup analysis revealed significant ethnicity-specific associations for <i>TaqI</i>, with stronger effects observed in Asian compared to Caucasian individuals. The trial sequential analysis indicated that additional studies are required to confirm the findings for <i>FokI</i>, while the recessive model of <i>TaqI</i> polymorphism showed a near-sufficient sample size for reliable conclusions. <i>Conclusions</i>: The <i>TaqI</i> polymorphism, particularly the tt genotype, appears to have a protective effect against LDH, especially in Asian populations and larger studies. However, further large-scale, multi-ethnic research is needed to confirm these findings and explore underlying biological mechanisms. |
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| ISSN: | 1010-660X 1648-9144 |