{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T03:04:25Z","timestamp":1779678265366,"version":"3.53.1"},"reference-count":78,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Vitamin D receptor (VDR) polymorphisms have been widely investigated as genetic determinants of neurodegenerative diseases, yet findings remain inconsistent and population-dependent. Evidence from the Middle East, North Africa, and T\u00fcrkiye (MENA&amp;T) regions, which is characterized by widespread vitamin D deficiency and distinct genetic backgrounds, has not been comprehensively synthesized. Methods: We conducted a systematic review and meta-analysis evaluating associations between four common VDR polymorphisms (ApaI rs7975232, FokI rs2228570, TaqI rs731236, and BsmI rs1544410) and the risk of multiple sclerosis (MS), Parkinson\u2019s disease (PD), and Alzheimer\u2019s disease (AD) in MENA&amp;T populations. Six databases were searched from inception to November 2025. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using fixed- and random-effects models across multiple genetic contrasts. Subgroup analyses by ethnicity were conducted for MS. Study quality was assessed using the Newcastle\u2013Ottawa Scale (NOS), and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: Nineteen unique case\u2013control studies (20 reports), including 4744 participants, were included. For MS, the ApaI polymorphism showed consistent associations with increased risk across genetic models (random-effects ORs = 1.4\u20131.9), with stronger effects in Arab and Iranian populations and no association in Turkish cohorts. FokI showed associations with MS under selected genetic models, particularly recessive and homozygous contrasts, although findings were not consistent across all analytical approaches. TaqI showed model-dependent associations with substantial heterogeneity, while BsmI showed no significant association. For AD, a meta-analysis of two studies showed no significant associations. For PD, ApaI showed associations with increased risk across several models without heterogeneity; however, these findings were based on a limited number of studies. Overall certainty of evidence ranged from very low to moderate. Conclusions: In MENA&amp;T populations, VDR ApaI polymorphism shows consistent evidence of association with MS susceptibility, while FokI may be associated under specific genetic models; evidence for AD and PD remains limited and should be considered exploratory. These findings highlight population-specific genetic heterogeneity and underscore the need for further large-scale studies to confirm these associations. These population-specific genetic associations underscore the importance of incorporating VDR genotyping into precision medicine frameworks for neurodegenerative disease risk stratification in MENA&amp;T populations, where vitamin D deficiency is highly prevalent.<\/jats:p>","DOI":"10.3390\/jpm16060277","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:07:47Z","timestamp":1779444467000},"page":"277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations of Vitamin D Receptor (ApaI, FokI, TaqI, BsmI) Polymorphisms with Neurodegenerative Diseases in the Middle East, North Africa and Turkiye (MENA&amp;T) Region: A Systematic Review and Meta-Analysis Toward Population-Specific Precision Medicine"],"prefix":"10.3390","volume":"16","author":[{"given":"Ahmed Abo","family":"Kalam","sequence":"first","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7709-5229","authenticated-orcid":false,"given":"Jameela","family":"Roshanuddin","sequence":"additional","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Qatar Preterm and Precision Medicine Research Clinic, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8814-7399","authenticated-orcid":false,"given":"BalaSubramani","family":"Gattu Linga","sequence":"additional","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Translational and Precision Medicine Research Lab, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0431-5744","authenticated-orcid":false,"given":"Faisal E.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Qatar Preterm and Precision Medicine Research Clinic, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Translational and Precision Medicine Research Lab, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Translational Research Institute (TRI), Hamad Medical Corporation (HMC), Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9753-3934","authenticated-orcid":false,"given":"Rand","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Faculty of Medicine, Qatar University, Doha 2713, Qatar"},{"name":"Department of Obstetrics and Gynecology, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeena Saeed","family":"BU Shurbak","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1317-0829","authenticated-orcid":false,"given":"Wael M. Y.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Basic Medical Science Department, Kulliyyah of Medicine, International Islamic University Malaysia (IIUM), Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-1135","authenticated-orcid":false,"given":"Nader","family":"Al-Dewik","sequence":"additional","affiliation":[{"name":"Department of Research, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Qatar Preterm and Precision Medicine Research Clinic, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Translational and Precision Medicine Research Lab, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Translational Research Institute (TRI), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Newborn Screening Unit, Neonatal Intensive Care Unit (NICU), Department of Pediatrics and Neonatology, Women\u2019s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha 3050, Qatar"},{"name":"Genomics and Precision Medicine (GPM), College of Health & Life Science (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar"},{"name":"Faculty of Health and Social Care Sciences, Kingston University, St. George\u2019s University of London, London KT1 2EE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1055\/s-0036-1579693","article-title":"Epidemiology of Multiple Sclerosis: From Risk Factors to Prevention\u2014An Update","volume":"36","author":"Ascherio","year":"2016","journal-title":"Semin. 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