Association Between the <i>FokI</i> and <i>ApaI</i> Polymorphisms in the Vitamin D Receptor Gene and Intervertebral Disc Degeneration: A Systematic Review and Meta-Analysis
Bibliographic record
Abstract
Background: Evidence supporting an association of intervertebral disc degeneration (DD) with polymorphisms of the vitamin D receptor (VDR) gene has been controversial. We performed a meta-analysis of these studies to determine if there was substantial evidence to support such an association between the VDR polymorphisms and DD. Methods: PubMed, Embase, and Science Direct databases were searched for studies that investigated associations of the FokI (rs2228570, rs10735810), and ApaI (rs7975253) polymorphisms of the VDR gene with DD. From the extracted genotype data from 14 publications, we estimated risk (odds ratio [OR] with 95% confidence intervals). Results: Overall associations of FokI with DD were absent (OR 0.96–1.04, p = 0.73–0.95) with heterogeneity in the dominant and codominant models (pheteroegeneity <0.10, I2 = 47–57%). Post-outlier pooled effects yielded dominant significance indicating reduced risk (OR 0.77, p = 0.01) with concomitant zero heterogeneity (I2 = 0%). ApaI effects pointed to reduced risks, with overall dominant significance (OR 0.69, p = 0.04) and Asian subgroup nonsignificance (OR 0.75–0.93, p = 0.17–0.74). In FokI, Non-Hispanic Caucasians (OR 0.77, p = 0.01) and males (OR 0.36–0.66, p = 0.001–0.04) were protected but not Hispanic Caucasians (OR 1.39–1.85, p = 0.006–0.05) and females (OR 1.72, p = 0.05). Tests of interaction between the genders highlighted female susceptibility and male protection (p = 0.001–0.005). Zero heterogeneity (I2 = 0%) is a key strength of these significant effects. Conclusion: This meta-analysis confirmed the protective role of the ApaI polymorphism, however, susceptibility and protective effects of the FokI polymorphism may be ethnic and gender specific.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.013 | 0.029 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.017 | 0.031 |
| Bibliometrics | 0.007 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".