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Systematic Review
Peer-Review Record

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

Medicina 2025, 61(5), 882; https://doi.org/10.3390/medicina61050882
by Alireza Sheikhi 1, Mohsen Nabiuni 1, Soha Zia 2, Masoud Sadeghi 3, Annette B. Brühl 4 and Serge Brand 4,5,6,7,8,9,*
Reviewer 1: Anonymous
Reviewer 2:
Medicina 2025, 61(5), 882; https://doi.org/10.3390/medicina61050882
Submission received: 22 March 2025 / Revised: 1 May 2025 / Accepted: 7 May 2025 / Published: 12 May 2025
(This article belongs to the Special Issue Neuromuscular Disorders: Diagnostical Approaches and Treatments)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article, Identifies TaqI as a potential biomarker for LDH risk, suggesting avenues for personalized medicine. Subgroup analyses highlight the protective role of TaqI in Asian populations, adding nuance to genetic associations. Here are my comments,

  1. Significant heterogeneity (up to 83%) in FokI analyses undermines confidence in pooled estimates.
  2. Some studies (e.g., Gaydarski 2023 for FokI) deviate from HWE, suggesting genotyping errors or population stratification.
  3. TSA reveals that sample sizes for FokIand some TaqI models fall below the required information size (RIS).
  4. FATHMM-XF predicts all variants (FokIApaITaqI) as "benign," contradicting the meta-analysis results for TaqI.
  5. No meta-regression for confounders (e.g., vitamin D levels, BMI, occupational factors).

Author Response

Dear Reviewer #1, thank you for all your kind efforts. Please find attached the detailed point-by-point-response.

Sincerely,

Serge Brand

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors
  • In the introduction I would add the percentage of cauda equina symptoms
  • - In the results Figure 1 19 records were excluded: can you explain the reason?

Author Response

Dear Reviewer #2; thank you for all your kind efforts. Please find attached the detailed point-by-point response.

Sincerely,

Serge Brand

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The revised version is suitable for publication.

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