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Acute Coronary Syndrome is associated with poor Vitamin D genes (CYP27B1, CYP24A1) – Nov 2019

Contribution of CYP27B1 and CYP24A1 genetic variations to the incidence of acute coronary syndrome and to vitamin D serum level

Canadian Journal of Physiology and Pharmacology, 2019, 97(12): 1152-1158, https://doi.org/10.1139/cjpp-2019-0258

Marina Sherif Fam,a Sally I. Hassanein,a Mohamed Farouk Abdel Rahman,b Reem Amr Assal,c Rasha Sayed Hanafi,d Mohamed Zakaria Gada

  • A Clinical Biochemistry Unit, Faculty of Pharmacy and Biotechnology, German University in Cairo, Fifth Settlement, Cairo, Egypt, 11432.
  • B Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th of October, Giza, Egypt, 12566.
  • C The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Fifth Settlement, Cairo, Egypt, 11432.
  • D Pharmaceutical Chemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Fifth Settlement, Cairo, Egypt, 11432.

Corresponding author: Marina Sherif Fam (email: marina.fam168 at gmail.com).
Copyright remains with the author(s) or their institution(s). Permission for reuse (free in most cases) can be obtained from RightsLink.

Cardiovascular diseases remain a major public health burden worldwide. It was reported that vitamin D protects the cardiovascular system through several mechanisms mainly by hindering atherosclerosis development. Genetic variations in vitamin D metabolic pathway were found to affect vitamin D levels. This study aimed at investigating the association between single nucleotide polymorphisms in genes involved in vitamin D metabolism, CYP27B and CYP24A1; 25-hydroxyvitamin D (25(OH)D) levels; and susceptibility to acute coronary syndrome (ACS). One hundred and eighty-five patients and 138 healthy controls were recruited. CYP24A1 rs2762939 was genotyped using fast real-time PCR, while CYP24A1 rs4809960 and CYP27B1 rs703842 were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism (PCR–RFLP). 25(OH)D3 and 25(OH)D2 levels were measured using ultra-performance liquid chromatography tandem mass spectrum. Vitamin D level was significantly lower in patients than controls (p < 0.05). The GG genotype of rs2762939 was significantly associated with the risk of ACS development, but not correlated to the vitamin D level. rs4809960 and rs703842 genetic variations were not associated with ACS nor with 25(OH)D level. The genetic variant rs2762939 of CYP24A1 is remarkably associated with ACS. Meanwhile, the variants rs4809960 and rs703842 are not associated with ACS incidence.


  • Abu el Maaty MA, Gad MZ. 2013. Vitamin D deficiency and cardiovascular disease: potential mechanisms and novel perspectives. J. Nutr. Sci. Vitaminol. 59(6): 479-488 Crossref, Medline, ISI, Google Scholar.
  • Abu el Maaty MA, Hassanein SI, Sleem HM, Gad MZ. 2015. Vitamin D receptor gene polymorphisms (TaqI and ApaI) in relation to 25-hydroxyvitamin D levels and coronary artery disease incidence. J. Recept. Signal Transduction 35(5): 391-395 Crossref, Medline, ISI, Google Scholar.
  • Abu el Maaty MA, Hassanein SI, Gad MZ. 2016. Genetic variation in vitamin D receptor gene (Fok1: rs2228570) is associated with risk of coronary artery disease. Biomarkers 21(1): 68-72 Crossref, Medline, ISI, Google Scholar.
  • Agnello L, Scazzone C, Sasso BL, Bellia C, Bivona G, Realmuto S, et al. 2017. VDBP, CYP27B1, and 25-hydroxyvitamin D gene polymorphism analyses in a group of Sicilian multiple sclerosis patients. Biochem. Genet. 55(2): 183-192 Crossref, Medline, ISI, Google Scholar.
  • Al Anouti F, Chehadeh SEH, Osman E, ElGhazali G, Al Safar H. 2017. Investigating the association of vitamin D metabolism genes CYP2R1, CYP24A1 and CYP27B1 with vitamin D status in young adult Emiratis. J. Food Nutr. Res. 5(1): 15-21 Google Scholar.
  • Bikle DD. 2014. Vitamin D metabolism, mechanism of action, and clinical applications. Chem. Biol. 21(3): 319-329 Crossref, Medline, Google Scholar.
  • DeLuca HF. 2014. History of the discovery of vitamin D and its active metabolites. Bonekey Rep. 3: 479 Crossref, Medline, Google Scholar.
  • Ellfolk M. 2008. Regulation of vitamin D 25-hydroxylases: effects of vitamin D metabolites and pharmaceutical compounds on the bioactivation of vitamin D. Acta Universitatis Upsaliensis. Google Scholar
  • Hibler EA, Klimentidis YC, Jurutka PW, Kohler LN, Lance P, Roe DJ, et al. 2015. CYP24A1 and CYP27B1 polymorphisms, concentrations of vitamin D metabolites, and odds of colorectal adenoma recurrence. Nutr. Cancer 67(7): 1131-1141 Crossref, Medline, ISI, Google Scholar.
  • Jiang T, Li L, Wang Y, Zhao C, Yang J, Ma D, et al. 2016. The association between genetic polymorphism rs703842 in CYP27B1 and multiple sclerosis: a meta-analysis. Medicine 95(19): e3612 Crossref, Medline, ISI, Google Scholar.
  • Jorde R, Schirmer H, Wilsgaard T, Joakimsen RM, Mathiesen EB, Njølstad I, et al. 2012. Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromsø Study. PloS ONE 7(5): e37295 Crossref, Medline, ISI, Google Scholar.
  • Judd SE, Tangpricha V. 2009. Vitamin D deficiency and risk for cardiovascular disease. Am. J. Med. Sci. 338(1): 40-44 Crossref, Medline, ISI, Google Scholar.
  • Kassi E, Adamopoulos C, Basdra EK, Papavassiliou AG. 2013. Role of vitamin D in atherosclerosis. Circulation 128(23): 2517-2531 Crossref, Medline, ISI, Google Scholar.
  • Kienreich K, Tomaschitz A, Verheyen N, Pieber T, Gaksch M, Grübler MR, Pilz S. 2013. Vitamin D and cardiovascular disease. Nutrients 5(8): 3005-3021 Crossref, Medline, ISI, Google Scholar.
  • Lewis CM, Knight J. 2012. Introduction to genetic association studies. Cold Spring Harb. Protoc. 2012(3): 297-306 Crossref, Medline, Google Scholar.
  • Menezes AR, Lamb MC, Lavie CJ, DiNicolantonio JJ. 2014. Vitamin D and atherosclerosis. Curr. Opin. Cardiol. 29(6): 571-577 Crossref, Medline, ISI, Google Scholar.
  • Morris HA, Anderson PH. 2010. Autocrine and paracrine actions of vitamin D. Citeseer. Google Scholar
  • Morrison MA, Silveira AC, Huynh N, Jun G, Smith SE, Zacharaki F, et al. 2011. Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration. Hum. Genomics 5(6): 538 Crossref, Medline, Google Scholar.
  • Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. 2016. Executive summary: Heart Disease and Stroke Statistics-2016 update: A report from the American Heart Association. Circulation 133(4): 447 Crossref, Medline, ISI, Google Scholar.
  • Nair R, Maseeh A. 2012. Vitamin D: The “sunshine” vitamin. J. Pharmacol. Pharmacother. 3(2): 118 Medline, Google Scholar.
  • Nissen J, Rasmussen LB, Ravn-Haren G, Andersen EW, Hansen B, Andersen R, et al. 2014. Common variants in CYP2R1 and GC genes predict vitamin D concentrations in healthy Danish children and adults. PloS ONE 9(2): e89907 Crossref, Medline, ISI, Google Scholar.
  • Pilz S, Gaksch M, O’Hartaigh B, Tomaschitz A, März W. 2013. The role of vitamin D deficiency in cardiovascular disease: where do we stand in 2013? Arch. Toxicol. 87(12): 2083-2103 Crossref, Medline, ISI, Google Scholar.
  • Ramnath N, Daignault-Newton S, Dy G, Muindi J, Adjei A, Elingrod V, et al. 2013. A phase I/II pharmacokinetic and pharmacogenomic study of calcitriol in combination with cisplatin and docetaxel in advanced non-small-cell lung cancer. Cancer Chemother. Pharmacol. 71(5): 1173-1182 Crossref, Medline, ISI, Google Scholar.
  • Reimers LL, Crew KD, Bradshaw PT, Santella RM, Steck SE, Sirosh I, et al. 2015. Vitamin D-related gene polymorphisms, plasma 25-hydroxyvitamin D, and breast cancer risk. Cancer Causes Control 26(2): 187-203 Crossref, Medline, ISI, Google Scholar.
  • Scazzone C, Agnello L, Ragonese P, Lo Sasso B, Bellia C, Bivona G, et al. 2018. Association of CYP2R1 rs10766197 with MS risk and disease progression. J. Neurosci. Res. 96(2): 297-304 Crossref, Medline, ISI, Google Scholar.
  • Scragg R, Jackson R, Holdaway IM, Lim T, Beaglehole R. 1990. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int. J. Epidemiol. 19(3): 559-563 Crossref, Medline, ISI, Google Scholar.
  • Sedky N, Rahman M, Hassanein S, Gad M. 2018. Genetic variants of CYP2R1 are key regulators of serum vitamin D levels and incidence of myocardial infarction in middle-aged Egyptians. Curr. Pharmaceut. Biotechnol. 19(3): 265-273 Crossref, Medline, ISI, Google Scholar.
  • Shen H, Bielak LF, Ferguson JF, Streeten EA, Yerges-Armstrong LM, Liu J, et al. 2010. Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification. Arterioscler. Thromb. Vasc. Biol. 30(12): 2648-2654 Crossref, Medline, ISI, Google Scholar.
  • Simon KC, Munger K, Kraft P, Hunter D, De Jager P, Ascherio A. 2011. Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis. J. Neurol. 258(9): 1676 Crossref, Medline, ISI, Google Scholar.
  • Sundqvist E, Bäärnhielm M, Alfredsson L, Hillert J, Olsson T, Kockum I. 2010. Confirmation of association between multiple sclerosis and CYP27B1. Eur. J. Hum. Genet. 18(12): 1349-1352 Crossref, Medline, ISI, Google Scholar.
  • Wang P, Zhang H, Zhang Z, Qin L, Li B. 2015. Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis. Onco Targets Ther. 8: 1175 Medline, ISI, Google Scholar.
  • Zhao Z, Winget M. 2011. Economic burden of illness of acute coronary syndromes: medical and productivity costs. BMC Health Serv. Res. 11(1): 35 Crossref, Medline, Google Scholar.

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