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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2025-05-01
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| author | Alireza Sheikhi Mohsen Nabiuni Soha Zia Masoud Sadeghi Annette B. Brühl Serge Brand |
| author_facet | Alireza Sheikhi Mohsen Nabiuni Soha Zia Masoud Sadeghi Annette B. Brühl Serge Brand |
| author_sort | Alireza Sheikhi |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-b36e1a0a3d6a4ebb840fa514dfd0fb3d |
| institution | DOAJ |
| issn | 1010-660X 1648-9144 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj-art-b36e1a0a3d6a4ebb840fa514dfd0fb3d2025-08-20T03:14:41ZengMDPI AGMedicina1010-660X1648-91442025-05-0161588210.3390/medicina61050882Association 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 PredictionAlireza Sheikhi0Mohsen Nabiuni1Soha Zia2Masoud Sadeghi3Annette B. Brühl4Serge Brand5Firoozgar Clinical Research Development Center (FCRDC), Iran University of Medical Sciences (IUMS), Tehran 1593748711, IranFiroozgar Clinical Research Development Center (FCRDC), Iran University of Medical Sciences (IUMS), Tehran 1593748711, IranDepartment of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran 1416634793, IranMedical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 671551616, IranCenter for Affective, Stress and Sleep Disorders, Psychiatric Clinics, University of Basel, 4002 Basel, SwitzerlandCenter for Affective, Stress and Sleep Disorders, Psychiatric Clinics, University of Basel, 4002 Basel, Switzerland<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.https://www.mdpi.com/1648-9144/61/5/882lumbar disc herniationvitamin D receptorgenetic polymorphismmeta-analysisallelic variation |
| spellingShingle | Alireza Sheikhi Mohsen Nabiuni Soha Zia Masoud Sadeghi Annette B. Brühl Serge Brand 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 Medicina lumbar disc herniation vitamin D receptor genetic polymorphism meta-analysis allelic variation |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | lumbar disc herniation vitamin D receptor genetic polymorphism meta-analysis allelic variation |
| url | https://www.mdpi.com/1648-9144/61/5/882 |
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