{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:45:22Z","timestamp":1791377122768,"version":"4.3.2"},"reference-count":87,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Natural Sciences and Engineering Research Council of Canada (NSERC)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin D (VD) plays a critical role in human health, with deficiencies linked to a range of adverse outcomes, including compromised immune function and increased disease risk. While environmental factors such as sunlight exposure and diet influence circulating VD levels, genetic variation is a significant and underappreciated contributor to interindividual differences in serum 25-hydroxyvitamin D [25(OH)D] concentrations. This review provides a comprehensive summary of genetic variants in key genes involved in VD synthesis (e.g., DHCR7, cyp2r1, cyp27b1), transport (GC), and metabolism (cyp24a1, cyp3a4), as well as in cholesterol transport proteins (SCARB1, CD36, NPC1L1). We examine how single-nucleotide polymorphisms (SNPs) and rare mutations in these genes affect enzyme activity, VD bioavailability, and overall 25(OH)D status. Importantly, we highlight evidence supporting gene-by-environment interactions and population-specific allele frequencies that further shape individual VD responses. In the context of clinical nutrition and precision health, these findings support the development of genomic risk scores (GRSs) to identify individuals at risk for deficiency or toxicity and guide personalized VD supplementation strategies. Regular monitoring of serum 25(OH)D alongside genetic screening may improve clinical outcomes by helping to achieve optimal VD immunosufficiency while minimizing the risk of adverse effects.<\/jats:p>","DOI":"10.3390\/nu17162673","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:56:06Z","timestamp":1755590166000},"page":"2673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetic Variants Influencing Individual Vitamin D Status"],"prefix":"10.3390","volume":"17","author":[{"given":"Niel A.","family":"Karrow","sequence":"first","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph, Guelph, ON N1G 2W1, Canada"},{"name":"Immunoceutica Inc., Cambridge, ON N1T 1N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6273-0815","authenticated-orcid":false,"given":"Spencer E.","family":"Leuschner","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-8485","authenticated-orcid":false,"given":"Umesh K.","family":"Shandilya","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-905X","authenticated-orcid":false,"given":"Bonnie A.","family":"Mallard","sequence":"additional","affiliation":[{"name":"Immunoceutica Inc., Cambridge, ON N1T 1N6, Canada"},{"name":"Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1695-7603","authenticated-orcid":false,"given":"Lauraine","family":"Wagter-Lesperance","sequence":"additional","affiliation":[{"name":"Immunoceutica Inc., Cambridge, ON N1T 1N6, Canada"},{"name":"Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8335-1118","authenticated-orcid":false,"given":"Byram W.","family":"Bridle","sequence":"additional","affiliation":[{"name":"Immunoceutica Inc., Cambridge, ON N1T 1N6, Canada"},{"name":"Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hribar, M., Hristov, H., Gregori\u010d, M., Blaznik, U., Zaletel, K., Oblak, A., Osredkar, J., Ku\u0161ar, A., \u017dmitek, K., and Rogelj, I. (2020). Nutrihealth Study: Seasonal Variation in Vitamin D Status Among the Slovenian Adult and Elderly Population. Nutrients, 12.","DOI":"10.3390\/nu12061838"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1529-8019.2009.01286.x","article-title":"Vitamin D Metabolism","volume":"23","author":"Lehmann","year":"2010","journal-title":"Dermatol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"582S","DOI":"10.1093\/ajcn\/88.2.582S","article-title":"Pharmacokinetics of Vitamin D Toxicity","volume":"88","author":"Jones","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wimalawansa, S.J. (2024). Physiology of Vitamin D-Focusing on Disease Prevention. Nutrients, 16.","DOI":"10.3390\/nu16111666"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2147\/PLMI.S373617","article-title":"Overcoming Infections Including COVID-19, by Maintaining Circulating 25(OH)D Concentrations Above 50 Ng\/mL","volume":"14","author":"Wimalawansa","year":"2022","journal-title":"Pathol. Lab. Med. Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wimalawansa, S.J. (2022). Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections\u2014Sepsis and COVID-19. Nutrients, 14.","DOI":"10.3390\/nu14142997"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1001\/jamasurg.2013.3176","article-title":"Association Between Preoperative 25-Hydroxyvitamin D Level and Hospital-Acquired Infections Following Roux-En-Y Gastric Bypass Surgery","volume":"149","author":"Quraishi","year":"2014","journal-title":"JAMA Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Borsche, L., Glauner, B., and von Mendel, J. (2021). COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 Ng\/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.1101\/2021.09.22.21263977"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Grant, W.B., Wimalawansa, S.J., Pludowski, P., and Cheng, R.Z. (2025). Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines. Nutrients, 17.","DOI":"10.3390\/nu17020277"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Grant, W.B., and Boucher, B.J. (2017). Randomized Controlled Trials of Vitamin D and Cancer Incidence: A Modeling Study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176448"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.eprac.2024.10.011","article-title":"Revisiting Vitamin D Guidelines: A Critical Appraisal of the Literature","volume":"30","author":"Holick","year":"2024","journal-title":"Endocr. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"McDonnell, S.L., Baggerly, C.A., French, C.B., Baggerly, L.L., Garland, C.F., Gorham, E.D., Hollis, B.W., Trump, D.L., and Lappe, J.M. (2018). Breast Cancer Risk Markedly Lower with Serum 25-Hydroxyvitamin D Concentrations \u226560 vs. <20 Ng\/Ml (150 vs. 50 Nmol\/L): Pooled Analysis of Two Randomized Trials and a Prospective Cohort. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199265"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1172\/JCI89031","article-title":"Early Pregnancy Vitamin D Status and Risk of Preeclampsia","volume":"126","author":"Mirzakhani","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, Treatment, and Prevention of Vitamin D Deficiency: An Endocrine Society Clinical Practice Guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1024\/0300-9831\/a000733","article-title":"Sources of Vitamin D for Humans","volume":"92","author":"Benedik","year":"2022","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2340\/00015555-0980","article-title":"Factors influencing vitamin D status","volume":"91","author":"Tsiaras","year":"2011","journal-title":"Acta Derm Venereol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Saponaro, F., Saba, A., and Zucchi, R. (2020). An Update on Vitamin D Metabolism. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186573"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14888","DOI":"10.1016\/S0021-9258(18)82416-4","article-title":"Kinetic and Thermodynamic Studies of the Conversion of Previtamin D3 to Vitamin D3 in Human Skin","volume":"268","author":"Tian","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1016\/j.jid.2024.04.022","article-title":"Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin","volume":"144","author":"Slominski","year":"2024","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.mce.2011.05.017","article-title":"Vitamin D Metabolism and Function in the Skin","volume":"347","author":"Bikle","year":"2011","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8363","DOI":"10.1074\/jbc.M115.699546","article-title":"Cholesterol-Mediated Degradation of 7-Dehydrocholesterol Reductase Switches the Balance from Cholesterol to Vitamin D Synthesis","volume":"291","author":"Prabhu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shin, M.H., Lee, Y., Kim, M.-K., Lee, D.H., and Chung, J.H. (2019). UV Increases Skin-Derived 1\u03b1,25-Dihydroxyvitamin D3 Production, Leading to MMP-1 Expression by Altering the Balance of Vitamin D and Cholesterol Synthesis from 7-Dehydrocholesterol. J. Steroid Biochem. Mol. Biol., 195.","DOI":"10.1016\/j.jsbmb.2019.105449"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jsbmb.2014.12.001","article-title":"Rapid Suppression of 7-Dehydrocholesterol Reductase Activity in Keratinocytes by Vitamin D","volume":"148","author":"Zou","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E15","DOI":"10.12788\/cutis.1019","article-title":"Exploring Skin Pigmentation Adaptation: A Systematic Review on the Vitamin D Adaptation Hypothesis","volume":"113","author":"Diehl","year":"2024","journal-title":"Cutis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/ajpa.24564","article-title":"The Evolution of Human Skin Pigmentation: A Changing Medley of Vitamins, Genetic Variability, and UV Radiation during Human Expansion","volume":"180","author":"Lucock","year":"2023","journal-title":"Am. J. Biol. Anthropol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/occmed\/kqt106","article-title":"Vitamin D Status of Canadians Employed in Northern Latitudes","volume":"63","author":"Chao","year":"2013","journal-title":"Occup. Med. (Lond)"},{"key":"ref_27","first-page":"433","article-title":"Effect of Latitude on Vitamin D Levels","volume":"117","author":"Leary","year":"2017","journal-title":"J. Am. Osteopath. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1080\/10408398.2020.1862753","article-title":"Functional Effects of Vitamin D: From Nutrient to Immunomodulator","volume":"62","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.foodchem.2014.09.021","article-title":"Fat-Soluble Vitamin Intestinal Absorption: Absorption Sites in the Intestine and Interactions for Absorption","volume":"172","author":"Goncalves","year":"2015","journal-title":"Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/mnfr.201000553","article-title":"Vitamin D Intestinal Absorption Is Not a Simple Passive Diffusion: Evidences for Involvement of Cholesterol Transporters","volume":"55","author":"Reboul","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bikle, D.D., and Schwartz, J. (2019). Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions. Front. Endocrinol. (Lausanne), 10.","DOI":"10.3389\/fendo.2019.00317"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109271","DOI":"10.1016\/j.steroids.2023.109271","article-title":"Genomic Signaling of Vitamin D","volume":"198","author":"Carlberg","year":"2023","journal-title":"Steroids"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"\u017bmijewski, M.A. (2022). Nongenomic Activities of Vitamin D. Nutrients, 14.","DOI":"10.3390\/nu14235104"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0955-2863(00)00077-2","article-title":"An Evaluation of the Biologic Activity and Vitamin D Receptor Binding Affinity of the Photoisomers of Vitamin D3 and Previtamin D3","volume":"11","author":"Chen","year":"2000","journal-title":"J. Nutr. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jsbmb.2013.10.012","article-title":"The Role of CYP11A1 in the Production of Vitamin D Metabolites and Their Role in the Regulation of Epidermal Functions","volume":"144 Pt A","author":"Slominski","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14467","DOI":"10.1074\/jbc.RA119.010173","article-title":"A Chromatin-Based Mechanism Controls Differential Regulation of the Cytochrome P450 Gene Cyp24a1 in Renal and Non-Renal Tissues","volume":"294","author":"Meyer","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Meyer, M.B., and Pike, J.W. (2020). Mechanistic Homeostasis of Vitamin D Metabolism in the Kidney through Reciprocal Modulation of Cyp27b1 and Cyp24a1 Expression. J. Steroid Biochem. Mol. Biol., 196.","DOI":"10.1016\/j.jsbmb.2019.105500"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155684","DOI":"10.1016\/j.prp.2024.155684","article-title":"Regulatory Mechanisms and Pathological Implications of CYP24A1 in Vitamin D Metabolism","volume":"264","author":"Milan","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1124\/dmd.111.041681","article-title":"Cytochrome P450 3A-Mediated Microsomal Biotransformation of 1\u03b1,25-Dihydroxyvitamin D3 in Mouse and Human Liver: Drug-Related Induction and Inhibition of Catabolism","volume":"40","author":"Deb","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1124\/mol.111.076356","article-title":"An Inducible Cytochrome P450 3A4-Dependent Vitamin D Catabolic Pathway","volume":"81","author":"Wang","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jsbmb.2012.09.012","article-title":"Interplay between Vitamin D and the Drug Metabolizing Enzyme CYP3A4","volume":"136","author":"Wang","year":"2013","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1021\/acschembio.6b00569","article-title":"Calcitroic Acid-A Review","volume":"11","author":"Yu","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/S0006-2952(00)00378-6","article-title":"Comparison of the Relative Effects of 1,24-Dihydroxyvitamin D(2) [1, 24-(OH)(2)D(2)], 1,24-Dihydroxyvitamin D(3) [1,24-(OH)(2)D(3)], and 1,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] on Selected Vitamin D-Regulated Events in the Rat","volume":"60","author":"Horst","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1093\/ajcn\/84.4.694","article-title":"The Case against Ergocalciferol (Vitamin D2) as a Vitamin Supplement","volume":"84","author":"Houghton","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1042\/bj20021651","article-title":"Hormonal Regulation of the Human Sterol 27-Hydroxylase Gene CYP27A1","volume":"372","author":"Araya","year":"2003","journal-title":"Biochem. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1194\/jlr.M600282-JLR200","article-title":"PXR Induces CYP27A1 and Regulates Cholesterol Metabolism in the Intestine","volume":"48","author":"Li","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17541","DOI":"10.1074\/jbc.M117.806901","article-title":"A Kidney-Specific Genetic Control Module in Mice Governs Endocrine Regulation of the Cytochrome P450 Gene Cyp27b1 Essential for Vitamin D3 Activation","volume":"292","author":"Meyer","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"bqae134","DOI":"10.1210\/endocr\/bqae134","article-title":"In Vivo Contribution of Cyp24a1 Promoter Vitamin D Response Elements","volume":"165","author":"Meyer","year":"2024","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jsbmb.2015.12.007","article-title":"Single Nucleotide Polymorphisms in the Vitamin D Pathway Associating with Circulating Concentrations of Vitamin D Metabolites and Non-Skeletal Health Outcomes: Review of Genetic Association Studies","volume":"164","author":"Jolliffe","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hypp\u00f6nen, E., Vimaleswaran, K.S., and Zhou, A. (2022). Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health. Nutrients, 14.","DOI":"10.3390\/nu14204408"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3945\/jn.112.172734","article-title":"CD36 and SR-BI Are Involved in Cellular Uptake of Provitamin A Carotenoids by Caco-2 and HEK Cells, and Some of Their Genetic Variants Are Associated with Plasma Concentrations of These Micronutrients in Humans","volume":"143","author":"Borel","year":"2013","journal-title":"J. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Galm\u00e9s, S., Serra, F., and Palou, A. (2018). Vitamin E Metabolic Effects and Genetic Variants: A Challenge for Precision Nutrition in Obesity and Associated Disturbances. Nutrients, 10.","DOI":"10.3390\/nu10121919"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zumaraga, M.P., Borel, P., Gleize, B., Nowicki, M., Ould-Ali, D., Landrier, J.-F., and Desmarchelier, C. (2024). Genetic Factors Contributing to Interindividual Variability of \u03b1-Tocopherol Levels in Subcutaneous Adipose Tissue among Healthy Adult Males. Nutrients, 16.","DOI":"10.2139\/ssrn.4865436"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/jcpt.12176","article-title":"Gene Polymorphism and Frequencies of the NPC1L1 Gene (Rs2072183, Rs217434 and Rs217428) in Japanese Patients with Dyslipidemia","volume":"39","author":"Kashiwabara","year":"2014","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1476-511X-11-61","article-title":"Association of Rs2072183 SNP and Serum Lipid Levels in the Mulao and Han Populations","volume":"11","author":"Miao","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/jhg.2009.18","article-title":"The g.-762T>C Polymorphism of the NPC1L1 Gene Is Common in Chinese and Contributes to a Higher Promoter Activity and Higher Serum Cholesterol Levels","volume":"54","author":"Chen","year":"2009","journal-title":"J. Hum. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Elkum, N., Alkayal, F., Noronha, F., Ali, M.M., Melhem, M., Al-Arouj, M., Bennakhi, A., Behbehani, K., Alsmadi, O., and Abubaker, J. (2014). Vitamin D Insufficiency in Arabs and South Asians Positively Associates with Polymorphisms in GC and CYP2R1 Genes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113102"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1007\/s00705-019-04378-8","article-title":"Impact of CYP2R1, CYP27A1 and CYP27B1 Genetic Polymorphisms Controlling Vitamin D Metabolism on Susceptibility to Hepatitis C Virus Infection in a High-Risk Chinese Population","volume":"164","author":"Yang","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.3803\/EnM.2021.1241","article-title":"Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study","volume":"36","author":"Kim","year":"2021","journal-title":"Endocrinol. Metab. (Seoul)"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"94","DOI":"10.18433\/jpps31305","article-title":"The CYP2R1 Enzyme: Structure, Function, Enzymatic Properties and Genetic Polymorphism","volume":"24","author":"Dong","year":"2021","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/0897190015585876","article-title":"Genetic Variation in CYP2R1 and GC Genes Associated With Vitamin D Deficiency Status","volume":"30","author":"Slater","year":"2017","journal-title":"J. Pharm. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"8289741","DOI":"10.1155\/2019\/8289741","article-title":"The Association between Polymorphisms of Vitamin D Metabolic-Related Genes and Vitamin D3 Supplementation in Type 2 Diabetic Patients","volume":"2019","author":"Hu","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"201","DOI":"10.22207\/JPAM.15.1.15","article-title":"Association of Single Nucleotide Polymorphisms in the VDR and CYP27B1 Genes with Risk of Developing Vitamin D3 Deficiency","volume":"15","author":"Selahvarzi","year":"2021","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Jarrar, Y., Alhammadin, G., and Lee, S.-J. (2025). Genetic Polymorphisms in Cytochrome P450 Enzymes Involved in Vitamin D Metabolism and the Vitamin D Receptor: Their Clinical Relevance. J. Pers. Med., 15.","DOI":"10.3390\/jpm15040128"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"109607","DOI":"10.1016\/j.steroids.2025.109607","article-title":"Genetic insights into vitamin D deficiency: A case-control study of GC and CYP24A1 gene polymorphism","volume":"218","author":"Usama","year":"2025","journal-title":"Steroids"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.nutres.2025.02.009","article-title":"Genetic Variants in Vitamin D Metabolism-Related Genes Are Associated with Vitamin D Status and Adiposity Markers","volume":"136","year":"2025","journal-title":"Nutr. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.clnesp.2022.07.018","article-title":"Genetic Factors Help Explain the Variable Responses of Young Children with Cystic Fibrosis to Vitamin D Supplements","volume":"51","author":"Lai","year":"2022","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.1038\/s41467-025-59132-3","article-title":"Drug-Induced Cis-Regulatory Elements in Human Hepatocytes Affect Molecular Phenotypes Associated with Adverse Reactions","volume":"16","author":"Wada","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Leszczy\u0144ska, D., Szatko, A., Latocha, J., Kochman, M., Duchnowska, M., W\u00f3jcicka, A., Misiorowski, W., Zgliczyn\u00edski, W., and Glinicki, P. (2024). Persistent Hypercalcaemia Associated with Two Pathogenic Variants in the CYP24A1 Gene and a Parathyroid Adenoma-a Case Report and Review. Front. Endocrinol. (Lausanne), 15.","DOI":"10.3389\/fendo.2024.1355916"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1172\/JCI98680","article-title":"CYP3A4 Mutation Causes Vitamin D-Dependent Rickets Type 3","volume":"128","author":"Roizen","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12263-020-00663-3","article-title":"Distribution of Variants in Multiple Vitamin D-Related Loci (DHCR7\/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXR\u03b1 and RXR\u03b3) Vary between European, East-Asian and Sub-Saharan African-Ancestry Populations","volume":"15","author":"Jones","year":"2020","journal-title":"Genes Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/tpj.2016.48","article-title":"Investigation of 7-Dehydrocholesterol Reductase Pathway to Elucidate off-Target Prenatal Effects of Pharmaceuticals: A Systematic Review","volume":"16","author":"Boland","year":"2016","journal-title":"Pharmacogenomics J."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Niforou, A., Konstantinidou, V., and Naska, A. (2020). Genetic Variants Shaping Inter-Individual Differences in Response to Dietary Intakes-A Narrative Review of the Case of Vitamins. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.558598"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kiourtzidis, M., K\u00fchn, J., Brandsch, C., and Stangl, G.I. (2020). Vitamin D Status of Mice Deficient in Scavenger Receptor Class B Type 1, Cluster Determinant 36 and ATP-Binding Cassette Proteins G5\/G8. Nutrients, 12.","DOI":"10.3390\/nu12082169"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Bouillon, R., Schuit, F., Antonio, L., and Rastinejad, F. (2020). Vitamin D Binding Protein: A Historic Overview. Front. Endocrinol. (Lausanne), 10.","DOI":"10.3389\/fendo.2019.00910"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/nbu.12656","article-title":"Association of Vitamin D-Binding Protein Polymorphisms and Serum 25(OH)D Concentration Varies among Chinese Healthy Infants of Different VDR-FokI Genotypes: A Multi-Centre Cross-Sectional Study","volume":"49","author":"Tsang","year":"2024","journal-title":"Nutr. Bull."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJMoa1807841","article-title":"Vitamin D-Binding Protein Deficiency and Homozygous Deletion of the GC Gene","volume":"380","author":"Henderson","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1210\/clinem\/dgaa056","article-title":"Differential Frequency of CYP2R1 Variants Across Populations Reveals Pathway Selection for Vitamin D Homeostasis","volume":"105","author":"Casella","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jsbmb.2016.07.014","article-title":"CYP2R1 Mutations Causing Vitamin D-Deficiency Rickets","volume":"173","author":"Thacher","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Norlin, M., and Wikvall, K. (2023). Enzymatic Activation in Vitamin D Signaling\u2014Past, Present and Future. Arch. Biochem. Biophys., 742.","DOI":"10.1016\/j.abb.2023.109639"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tran, T.A.T., Dien, T.M., Nguyen, N.L., Nguyen, K.N., Can, T.B.N., Thao, B.P., Hong, N.T.T., Tran, V.K., Tran, T.H., and Khoa, N.X. (2025). Phenotypes and Genotypes of Children with Vitamin D-Dependent Rickets Type 1A: A Single Tertiary Pediatric Center in Vietnam. Diagnostics, 15.","DOI":"10.20944\/preprints202502.2177.v1"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s00467-018-4030-3","article-title":"Drug-Metabolizing Enzymes CYP3A as a Link between Tacrolimus and Vitamin D in Renal Transplant Recipients: Is It Relevant in Clinical Practice?","volume":"34","author":"Cransberg","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e35058","DOI":"10.1016\/j.heliyon.2024.e35058","article-title":"A CYP11A1 Homozygous Exonic Variant Inducing an Alternative Splicing, Frameshift and Truncation in a Family with Congenital Adrenal Hyperplasia","volume":"10","author":"Alhamoudi","year":"2024","journal-title":"Heliyon"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Goursaud, C., Mallet, D., Janin, A., Menassa, R., Tardy-Guidollet, V., Russo, G., Lienhardt-Roussie, A., Lecointre, C., Plotton, I., and Morel, Y. (2018). Aberrant Splicing Is the Pathogenicity Mechanism of the p.Glu314Lys Variant in CYP11A1 Gene. Front. Endocrinol. (Lausanne), 9.","DOI":"10.3389\/fendo.2018.00491"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.bbi.2024.07.012","article-title":"Placenta-Specific CYP11A1 Overexpression Lead to Autism-like Symptom in Offspring with Altered Steroid Hormone Biosynthesis in the Placenta-Brain Axis and Rescued by Vitamin D Intervention","volume":"121","author":"Yin","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1186\/s13063-024-08461-7","article-title":"Rapid Normalization of Vitamin D Deficiency in PICU (VITdALIZE-KIDS): Study Protocol for a Phase III, Multicenter Randomized Controlled Trial","volume":"25","author":"Menon","year":"2024","journal-title":"Trials"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Helmeczi, E., Pandya, H., O\u2019Hearn, K., McNally, D., and Britz-McKibbin, P. (2025). Treatment Response Variations to a Single Large Bolus of Enteral Cholecalciferol in Vitamin D Deficient Critically Ill Children: Metabolomic Insights for Precision Nutrition. J. Steroid Biochem. Mol. Biol., 250.","DOI":"10.1016\/j.jsbmb.2025.106720"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/16\/2673\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:30:31Z","timestamp":1760034631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/16\/2673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":87,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["nu17162673"],"URL":"https:\/\/doi.org\/10.3390\/nu17162673","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,19]]}}}