Links between vitamin D receptor gene polymorphisms and coronary artery disease: a review of evidence

Authors

  • M. Maruf-Ur-Rahman Department of Biochemistry, Dhaka National Medical College, Dhaka, Bangladesh
  • M. Rafiqul Islam Department of Biochemistry and Molecular Biology, Jagannath University, Dhaka, Bangladesh
  • Wazeda Begum Department of Dermatology and Venereology, Dhaka National Medical College, Dhaka, Bangladesh
  • M. Shafiqul Islam Department of Biochemistry and Molecular Biology, Ibn Sina Diagnostic Lab and Consultation Centre, Jatrabari, Dhaka, Bangladesh
  • Hosne Ara Department of Molecular Biology, Central Dogma Lab, Invent Technologies Ltd., Dhaka, Bangladesh

DOI:

https://doi.org/10.18203/2320-6012.ijrms20253208

Keywords:

Coronary artery disease, Single-nucleotide polymorphisms, Vitamin D receptor, Vitamin D receptor gene

Abstract

Vitamin D receptor (VDR) serves as a nuclear receptor, playing a significant role in mediating the physiological effects of vitamin D through the regulation of gene expression. Polymorphisms in the VDR gene have the potential impact on receptor activity through modifications in gene transcription, mRNA stability and protein function. Within the extensive array of single-nucleotide polymorphisms (SNPs) identified in the VDR gene, which exceeds 470, four specific variants have captured significant scientific attention: FokI (rs2228570), ApaI (rs7975232), BsmI (rs1544410) and TaqI (rs731236). The examination of these polymorphisms has been conducted within the framework of various diseases, such as malignancies, diabetes mellitus, myocardial infarction and coronary artery disease (CAD). Numerous studies indicate a possible links between these genetic variants and an increased risk of developing CAD; however, discrepancies in findings across various populations and research methodologies persist. This review will thoroughly overview the existing literature regarding the links between VDR polymorphisms and CAD.

Metrics

Metrics Loading ...

References

Ezzat H, Attia FA, Mokhtar A, El-Tokhy HM, Alalfy MN, Elkhouly NY. Prevalence of thrombophilic gene polymorphisms (FVL G1691A and MTHFR C677T) in patients with myocardial infarction. Egyptian J Med Human Gen. 2014;1;15(2):113–23. DOI: https://doi.org/10.1016/j.ejmhg.2014.02.001

Miyabe M, Ohashi K, Shibata R, Uemura Y, Ogura Y, Yuasa D, et al. Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury. Cardiovasc Res. 2014;103(1):111–20. DOI: https://doi.org/10.1093/cvr/cvu105

Gilbert K, Malick M, Madingou N, Touchette C, Bourque-Riel V, Tomaro L, et al. Metabolites derived from omega-3 polyunsaturated fatty acids are important for cardioprotection. Eur J Pharmacol. 2015;769:147–53. DOI: https://doi.org/10.1016/j.ejphar.2015.11.010

Uçar F, Celik S, Yücel B, Sönmez M, Celep F, Erkut N. MTHFR C677T polymorphism and its relationship to myocardial infarction in the Eastern Black Sea region of Turkey. Arch Med Res. 2011;42(8):709–12. DOI: https://doi.org/10.1016/j.arcmed.2011.12.007

Dogra RK, Das R, Ahluwalia J, Kumar RM, Talwar KK. Prothrombotic gene polymorphisms and plasma factors in young North Indian survivors of acute myocardial infarction. J Thromb Thrombolysis. 2012;34(2):276–82. DOI: https://doi.org/10.1007/s11239-012-0734-6

Szabó GV, Kunstár A, Acsády G. Methylentetrahydrofolate reductase and nitric oxide synthase polymorphism in patients with atherosclerosis and diabetes. Pathol Oncol Res. 2009;15(4):631–7. DOI: https://doi.org/10.1007/s12253-009-9163-z

Onrat ST, Akci O, Söylemez Z, Onrat E, Avşar A. Prevalence of myocardial infarction polymorphisms in Afyonkarahisar, Western Turkey. Mol Biol Rep. 2012;39(9):9257–64. DOI: https://doi.org/10.1007/s11033-012-1799-1

Isordia-Salas I, Trejo-Aguilar A, Valadés-Mejía MG, Santiago-Germán D, Leaños-Miranda A, Mendoza-Valdéz L, et al. C677T polymorphism of the 5,10 MTHFR gene in young Mexican subjects with ST-elevation myocardial infarction. Arch Med Res. 2010;41(4):246–50. DOI: https://doi.org/10.1016/j.arcmed.2010.04.008

Prabhakar P, Majumdar V, Kulkarni GB, Christopher R. Genetic variants of vitamin D receptor and susceptibility to ischemic stroke. Biochem Biophys Res Commun. 2015;456(2):631–6. DOI: https://doi.org/10.1016/j.bbrc.2014.12.007

Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014;114(2):379–93. DOI: https://doi.org/10.1161/CIRCRESAHA.113.301241

Pike JW, Meyer MB. The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D(3). Endocrinol Metab Clin North Am. 2010;39(2):255–69. DOI: https://doi.org/10.1016/j.ecl.2010.02.007

Artaza JN, Contreras S, Garcia LA, Mehrotra R, Gibbons G, Shohet R, et al. Vitamin D and Cardiovascular Disease: Potential Role in Health Disparities. J Health Care Poor Underserved. 2011;22(4):23–38. DOI: https://doi.org/10.1353/hpu.2011.0161

Al Mheid I, Quyyumi AA. Vitamin D and Cardiovascular Disease: Controversy Unresolved. J Am Coll Cardiol. 2017;70(1):89–100. DOI: https://doi.org/10.1016/j.jacc.2017.05.031

Marcinkowska E. A run for a membrane vitamin D receptor. Biol Signals Recept. 2001;10(6):341–9. DOI: https://doi.org/10.1159/000046902

Maia J, da Silva AS, do Carmo RF, de Mendonça TF, Griz LHM, Moura P, et al. The association between vitamin D receptor gene polymorphisms (TaqI and FokI), Type 2 diabetes and micro-/macrovascular complications in postmenopausal women. Appl Clin Genet. 2016;9:131–6. DOI: https://doi.org/10.2147/TACG.S101410

Uitterlinden AG, Fang Y, Van Meurs JBJ, Pols HAP, Van Leeuwen JPTM. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;1;338(2):143–56. DOI: https://doi.org/10.1016/j.gene.2004.05.014

Lin CH, Chen KH, Chen ML, Lin HI, Wu RM. Vitamin D receptor genetic variants and Parkinson’s disease in a Taiwanese population. Neurobiol Aging. 2014;35(5):11-3. DOI: https://doi.org/10.1016/j.neurobiolaging.2013.10.094

Rivera-Leon EA, Palmeros-Sanchez B, Llamas-Covarrubias IM, Fernandez S, Armendariz-Borunda J, Gonzalez-Hita M, et al. Vitamin-D receptor gene polymorphisms (TaqI and ApaI) and circulating osteocalcin in type 2 diabetic patients and healthy subjects. Endokrynol Pol. 2015;66(4):329–33. DOI: https://doi.org/10.5603/EP.2015.0042

Alizadeh S, Djafarian K, Alizadeh H, Mohseni R, Shab-Bidar S. Common Variants of Vitamin D Receptor Gene Polymorphisms and Susceptibility to Coronary Artery Disease: A Systematic Review and Meta-Analysis. J Nutrigenet Nutrigenomics. 2017;10(1–2):9–18. DOI: https://doi.org/10.1159/000455914

Moradi N, Fadaei R, Ahmadi R, Mohammad MH, Shahmohamadnejad S, Tavakoli-Yaraki M, et al. Role of serum MMP-9 levels and vitamin D receptor polymorphisms in the susceptibility to coronary artery disease: An association study in Iranian population. Gene. 2017;10;628:295–300. DOI: https://doi.org/10.1016/j.gene.2017.07.060

Yao M, Oduro PK, Akintibu AM, Yan H. Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases. Front Pharmacol. 2024;15:54. DOI: https://doi.org/10.3389/fphar.2024.1298181

Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson K, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5(6):819–29. DOI: https://doi.org/10.1161/CIRCOUTCOMES.112.967604

Zmuda JM, Cauley JA, Ferrell RE. Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev. 2000;22(2):203–17. DOI: https://doi.org/10.1093/oxfordjournals.epirev.a018033

Vélayoudom-Céphise FL, Larifla L, Donnet JP, Maimaitiming S, Deloumeaux J, Blanchet A, et al. Vitamin D deficiency, vitamin D receptor gene polymorphisms and cardiovascular risk factors in Caribbean patients with type 2 diabetes. Diabetes Metab. 2011;37(6):540–5. DOI: https://doi.org/10.1016/j.diabet.2011.05.005

Dorsch MP, Nemerovski CW, Ellingrod VL, Cowger JA, Dyke DB, Koelling TM, et al. Vitamin D Receptor Genetics on Extracellular Matrix Biomarkers and Hemodynamics in Systolic Heart Failure. J Cardiovasc Pharmacol Ther. 2014;19(5):439–45. DOI: https://doi.org/10.1177/1074248413517747

Sygitowicz G, Pera Ł, Sitkiewicz D. Vitamin D receptor (VDR) polymorphism and the risk of cardiovascular events. Polish Heart Journal (Kardiologia Polska). 2014;72(1):64–6. DOI: https://doi.org/10.5603/KP.2014.0005

Barakat K, Hitman GA. The emerging role of vitamin D and its receptor in the pathogenesis of acute coronary syndromes. British J Cardiol. 2006;13(1):9.

Krishna SM. Vitamin D as A Protector of Arterial Health: Potential Role in Peripheral Arterial Disease Formation. Int J Mol Sci. 2019;20(19):4907. DOI: https://doi.org/10.3390/ijms20194907

Umar M, Sastry KS, Chouchane AI. Role of Vitamin D Beyond the Skeletal Function: A Review of the Molecular and Clinical Studies. Int J Mol Sci. 2018;19(6):1618. DOI: https://doi.org/10.3390/ijms19061618

Duplancic D, Cesarik M, Poljak NK, Radman M, Kovacic V, Radic J, et al. The influence of selective vitamin D receptor activator paricalcitol on cardiovascular system and cardiorenal protection. Clin Interv Aging. 2013;8:149–56. DOI: https://doi.org/10.2147/CIA.S38349

Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29(6):726–76. DOI: https://doi.org/10.1210/er.2008-0004

Sangkaew B, Nuinoon M, Jeenduang N. Association of vitamin D receptor gene polymorphisms with serum 25(OH)D levels and metabolic syndrome in Thai population. Gene. 2018;659:59–66. DOI: https://doi.org/10.1016/j.gene.2018.03.047

Vaidya A, Sun B, Forman JP, Hopkins PN, Brown NJ, Kolatkar NS, et al. The Fok1 vitamin D receptor gene polymorphism is associated with plasma renin activity in Caucasians. Clin Endocrinol (Oxf). 2011;74(6):783–90. DOI: https://doi.org/10.1111/j.1365-2265.2011.03991.x

Hong YJ, Kang ES, Ji MJ, Choi HJ, Oh T, Koong SS, et al. Association between Bsm1 Polymorphism in Vitamin D Receptor Gene and Diabetic Retinopathy of Type 2 Diabetes in Korean Population. Endocrinol Metab (Seoul). 2015;30(4):469–74. DOI: https://doi.org/10.3803/EnM.2015.30.4.469

Szeto FL, Reardon CA, Yoon D, Wang Y, Wong KE, Chen Y, et al. Vitamin D receptor signaling inhibits atherosclerosis in mice. Mol Endocrinol. 2012;26(7):1091–101. DOI: https://doi.org/10.1210/me.2011-1329

Imani D, Razi B, Khosrojerdi A, Lorian K, Motallebnezhad M, Rezaei R, et al. Vitamin D receptor gene polymorphisms and susceptibility to urolithiasis: a meta-regression and meta-analysis. BMC Nephrol. 2020;21(1):263. DOI: https://doi.org/10.1186/s12882-020-01919-1

Deng H, Liu F, Pan Y, Jin X, Wang H, Cao J. BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor gene and periodontitis: a meta-analysis of 15 studies including 1338 cases and 1302 controls. J Clin Periodontol. 2011;38(3):199–207. DOI: https://doi.org/10.1111/j.1600-051X.2010.01685.x

Abouzid M, Kruszyna M, Burchardt P, Kruszyna Ł, Główka FK, Karaźniewicz-Łada M. Vitamin D Receptor Gene Polymorphism and Vitamin D Status in Population of Patients with Cardiovascular Disease-A Preliminary Study. Nutrients. 2021;13(9):3117. DOI: https://doi.org/10.3390/nu13093117

Raljević D, Peršić V, Markova-Car E, Cindrić L, Miškulin R, Žuvić M, et al. Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease. BMC Cardiovasc Disord. 2021;21(1):188. DOI: https://doi.org/10.1186/s12872-021-01959-x

Pan XM, Li DR, Yang L, Wang EY, Chen TY, Liu YJ, et al. No association between vitamin D receptor polymorphisms and coronary artery disease in a Chinese population. DNA Cell Biol. 2009;28(10):521–5. DOI: https://doi.org/10.1089/dna.2009.0908

He L, Wang M. Association of vitamin d receptor-a gene polymorphisms with coronary heart disease in Han Chinese. Int J Clin Exp Med. 2015;8(4):6224–9.

Lu S, Guo S, Hu F, Guo Y, Yan L, Ma W, et al. The Associations Between the Polymorphisms of Vitamin D Receptor and Coronary Artery Disease. Medicine (Baltimore). 2016;95(21):3467. DOI: https://doi.org/10.1097/MD.0000000000003467

Van Schooten FJ, Hirvonen A, Maas LM, De Mol BA, Kleinjans JC, Bell DA, et al. Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking and aromatic DNA adduct levels in human right atrial tissue. FASEB J. 1998;12(13):1409–17. DOI: https://doi.org/10.1096/fasebj.12.13.1409

Ortlepp JR, Lauscher J, Hoffmann R, Hanrath P, Joost HG. The vitamin D receptor gene variant is associated with the prevalence of type 2 diabetes mellitus and coronary artery disease. Diabet Med. 2001;18(10):842–5. DOI: https://doi.org/10.1046/j.1464-5491.2001.00585.x

Ortlepp JR, von Korff A, Hanrath P, Zerres K, Hoffmann R. Vitamin D receptor gene polymorphism BsmI is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of 3441 patients. Eur J Clin Invest. 2003;33(2):106–9. DOI: https://doi.org/10.1046/j.1365-2362.2003.01124.x

Ferrarezi D, Bellili-Muñoz N, Dubois-Laforgue D, Cheurfa N, Lamri A, Reis AF, et al. Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: the DIABHYCAR prospective study. Diabetes Metab. 2013;39(3):263–70. DOI: https://doi.org/10.1016/j.diabet.2012.11.004

Abu el Maaty MA, Hassanein SI, Sleem HM, Gad MZ. Vitamin D receptor gene polymorphisms (TaqI and ApaI) in relation to 25-hydroxyvitamin D levels and coronary artery disease incidence. J Recept Signal Transduct Res. 2015;35(5):391–5. DOI: https://doi.org/10.3109/10799893.2014.959593

Eweida SM, Salem A, Shaker YM, Samy N, Yassen I, Mohamed RH. Vitamin D levels and vitamin D receptor genetic variants in Egyptian cardiovascular disease patients with and without diabetes. Egyptian Journal of Medical Human Genetics. 2021;10;22(1):55. DOI: https://doi.org/10.1186/s43042-021-00174-9

Tabaei S, Motallebnezhad M, Tabaee SS. Vitamin D Receptor (VDR) Gene Polymorphisms and Risk of Coronary Artery Disease (CAD): Systematic Review and Meta-analysis. Biochem Genet. 2021;59(4):813–36. DOI: https://doi.org/10.1007/s10528-021-10038-x

Downloads

Published

2025-09-29

How to Cite

Maruf-Ur-Rahman, M., Islam, M. R., Begum, W., Islam, M. S., & Ara, H. (2025). Links between vitamin D receptor gene polymorphisms and coronary artery disease: a review of evidence. International Journal of Research in Medical Sciences, 13(10), 4458–4464. https://doi.org/10.18203/2320-6012.ijrms20253208

Issue

Section

Review Articles