# Association of VDR Polymorphisms (FokI, ApaI, and TaqI) with Susceptibility to Lumbar Disc Herniation: Systematic Review, Meta-Analysis, Trial Sequential Analysis, and Transcriptional Prediction

## TL;DR

This study finds that a specific vitamin D receptor gene variant, TaqI, may protect against lumbar disc herniation, especially in Asian populations.

## Contribution

The study provides the first meta-analysis and trial sequential analysis of VDR polymorphisms in relation to lumbar disc herniation.

## Key findings

- TaqI polymorphism showed a protective effect against lumbar disc herniation, particularly in Asian populations.
- FokI and ApaI polymorphisms were not significantly associated with lumbar disc herniation risk.
- Subgroup analysis revealed stronger effects of TaqI in larger studies and among Asian individuals.

## Abstract

Background and Objectives: Lumbar disc herniation (LDH) is influenced by genetic, mechanical, and behavioral factors, with genetic predisposition playing a key role. Vitamin D receptor (VDR) polymorphisms have been implicated in LDH susceptibility, warranting further investigation. This study aimed to assess the association between VDR polymorphisms (FokI, ApaI, and TaqI) and LDH risk through a systematic review, meta-analysis, and trial sequential analysis (TSA). Materials and Methods: 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 I2 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. Results: From 79 records, 10 studies were entered into the meta-analysis. The meta-analysis results showed no significant association of FokI and ApaI polymorphisms with LDH, while TaqI exhibited a protective effect, particularly in Asian populations and larger studies. The subgroup analysis revealed significant ethnicity-specific associations for TaqI, 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 FokI, while the recessive model of TaqI polymorphism showed a near-sufficient sample size for reliable conclusions. Conclusions: The TaqI 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.