Vitamin D levels and vitamin D receptor genetic variants in Egyptian cardiovascular disease patients with and without diabetes

Soad M. Eweida1, Ahmed M. Salem2, Yehia Shaker1, Nervana Samy1, Ibrahim Yassen3, Rania Hassan Mohamed2
1Department of Biochemistry, National Research Centre, Dokki, Giza, Egypt
2Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
3Department of Cardiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

Tóm tắt

Abstract Background 25-Hydroxyvitamin D (Vit.D) levels associated with cardiovascular disease (CVD) may vary according to genetic variants in the vitamin D receptor (VDR) gene. However, the existing results are not conclusive in the Egyptian population, where diabetes mellitus is a common CVD risk factor. The purpose of the study was to evaluate the role of VDR polymorphism in Egyptian patients with CVD by studying the association of the rs2228570 (FokI) and rs1544410 (BsmI) single nucleotide polymorphisms (SNPs) of the VDR gene and serum levels of Vit.D with several CVD risk factors in patients with and without diabetes mellitus. We studied the genotypes for rs2228570 (FokI) and rs1544410 (BsmI) SNPs of the VDR gene in 382 Egyptian patients (120 CVD patients with diabetes, 124 CVD patients without diabetes, 69 diabetic patients without CVD and 69 healthy individuals). We also determined the serum levels of Vit.D, insulin, lipids, fasting blood glucose (FBG), and the body mass index (BMI). Results The distribution of genotypes and allelic frequencies of the rs2228570 (FokI) and rs1544410 (BsmI) SNPs of the VDR gene was significant in CVD patients (p < 0.001). The level of Vit.D was significantly lower in patients with CVD and diabetes compared to those without diabetes (p < 0.001). Moreover, there was a significant association between Vit.D level and the selected SNPs with serum lipids, BMI, FBG, and insulin levels in CVD patients with or without diabetes. Conclusion The level of Vit.D and the distribution of VDR polymorphisms are associated with risk of CVD in Egyptian patients with or without diabetes. These results suggest that VDR polymorphisms may be potential diagnostic biomarkers for CVD susceptibility.

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Tài liệu tham khảo

Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, Mladěnka A, Karlíčková J, Jahodář L, Vopršalová M, Varner KJ, Štěrba M, TOX-OER and CARDIOTOX Hradec Králové Researchers and Collaborators (2018) Comprehensive review of cardiovascular toxicity of drugs and related agents. Med Res Rev 38(4):1332–1403. https://doi.org/10.1002/med.21476

Teo K, Dokainish H (2017) The emerging epidemic of cardiovascular risk factors and atherosclerotic disease in developing countries. Can J Cardiol 33(3):358–365. https://doi.org/10.1016/j.cjca.2016.12.014

World Health Organization. WHO (2017) Cardiovascular diseases (CVDs). Available from: http://www.who.int/cardiovascular_diseases/en/.

World Health Organization (2018) Egypt: World Health Organization—noncommunicable diseases (NCD) country profiles, Availablefrom: https://www.who.int/nmh/countries/2018/egy_en.pdf?ua=1.

Bhatnagar A (2017) Environmental determinants of cardiovascular disease. Circ Res 121(2):162–180. https://doi.org/10.1161/CIRCRESAHA.117.306458

Laakso M, Kuusisto J (2014) Insulin resistance and hyperglycaemia in cardiovascular disease development. Nature Reviews Endocrinology 10(5):293–302. https://doi.org/10.1038/nrendo.2014.29

Fiatal S, Ádány R (2018) Application of single-nucleotide polymorphism-related risk estimates in identification of increased genetic susceptibility to cardiovascular diseases: a literature review. Front Public Health 358(5). https://doi.org/10.3389/fpubh.2017.00358

Skaaby T, Thuesen BH, Linneberg A (2017) Vitamin D, cardiovascular disease and risk factors. Dv Exp Med Biol 996:221–230. https://doi.org/10.1007/978-3-319-56017-5_18

Wimalawansa S (2018) Vitamin D and cardiovascular diseases: causality. J Steroid BiochemMolBiol 175:29–43. https://doi.org/10.1016/j.jsbmb.2016.12.016

Lv L, Tan X, Peng X, Bai R, Xiao Q, Zou T, Tan J, Zhang H, Wang C (2020) The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson’s disease. TranslNeurodegener 9(34):34. https://doi.org/10.1186/s40035-020-00213-2

Szymczak-Pajor I, Śliwińska A (2019) Analysis of association between vitamin D deficiency and insulin resistance. Nutrients 11(4):794. https://doi.org/10.3390/nu11040794

VimaleswaranKS PC, Hyppönen E (2014) Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes. Diabetes Metab 40(5):386–395. https://doi.org/10.1016/j.diabet.2014.01.003

Jain R, Von Hurst PR, Stonehouse W et al (2012) Association of vitamin D receptor gene polymorphisms with insulin resistance and response to vitamin D. Metabolism 61(3):293–301. https://doi.org/10.1016/j.metabol.2011.06.018

Zaki M, Kamal S, Basha WA, Youness E, Ezzat W, el-Bassyouni H, Amr K (2017) Association of vitamin D receptor gene polymorphism (VDR) with vitamin D deficiency, metabolic and inflammatory markers in Egyptian obese women. Genes & Diseases 4(3):176–182. https://doi.org/10.1016/j.gendis.2017.07.002

Shen F, Guo C, Wang Y, Yu F, Zhang D, Liu X, Ba Y, Wang C, Li W, Li X (2020) Lowserum 25-hydroxyvitamin D levels may increase the detrimental effect of VDR variants on the risk of essential hypertension. Eur J ClinNutr 74:1091–1099. https://doi.org/10.1038/s41430-019-0543-5

Maia J, Da Silva AS, Do Carmo RF et al (2016) The association between vitamin D receptor gene polymorphisms (TaqI and FokI), Type 2 diabetes, and micro-/macrovascular complications in postmenopausal women. Appl Clin Genet 9:131–136. https://doi.org/10.2147/TACG.S101410

Hassan I, Bhat YJ, Majid S et al (2019) Association of vitamin D receptor gene polymorphisms and serum 25-hydroxy vitamin D levels in vitiligo - a case-control study. Indian Dermatol Online J10 2:131–138. https://doi.org/10.4103/idoj.IDOJ_97_18

Ortlepp JR, Lauscher J, Hoffmann R, Hanrath P, Joost HG (2001) The VDR gene variant is associated with the prevalence of Type 2 diabetes mellitus and coronary artery disease. Diabet Med 18(10):842–845. https://doi.org/10.1046/j.1464-5491.2001.00585.x

Ferrarezi DA, Bellili-Muñoz N, Dubois-Laforgue D et al (2013) 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 39(3):263–270

JiaJ TY, Shen C et al (2018) Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population. Lipids Health Dis 17(193) https://doi.org/10.1186/s12944-018-0819-0:193

Nakhl S, Sleilaty G, Chouery E et al (2019) FokI vitamin D receptor gene polymorphism and serum 25-hydroxyvitamin D in patients with cardiovascular risk. Arch Med SciAtheroscler Dis 4:e298–e303

Pan XM, Li DR, Yang L, Wang EY, Chen TY, Liu YJ, Liu M, Liao ZG (2009) No association between vitamin D receptor polymorphisms and coronary artery disease in a Chinese population. DNA Cell Biol 28(10):521–525. https://doi.org/10.1089/dna.2009.0908

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

World Health Organization (2007) Prevention of cardiovascular disease: guidelines for assessment and management of cardiovascular risk. World Health Organization https://apps.who.int/iris/handle/10665/43685

American Diabetes Association (2014) Standards of medical care in diabetes- 2014. Diabetes care 37(Suppl 1):S14–S80. https://doi.org/10.2337/dc14-S014

Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 18(6):499–502. https://doi.org/10.1093/clinchem/18.6.499

Nargesi AA, Heidari B, Esteghamati S, Hafezi-Nejad N, Sheikhbahaei S, Pajouhi A, Nakhjavani M, Esteghamati A (2016) Contribution of vitamin D deficiency to the risk of coronary heart disease in subjects with essential hypertension. Atherosclerosis 244:165–171. https://doi.org/10.1016/j.atherosclerosis.2015.11.020

Chen XE, Chen P, Chen SS, Lu J, Ma T, Shi G, Zhou Y, Li J, Sheng L (2017) A population association study of vitamin D receptor gene polymorphisms and haplotypes with the risk of systemic lupus erythematosus in a Chinese population. Immunol Res 65(3):750–756. https://doi.org/10.1007/s12026-017-8914-2

Cohen J (1988) Statistical power analysis for the behavioral sciences. Lawrence Erlbaum Associates, Hillsdale, New Jersey

Dawson B, Trapp RG (2001) Basic & clinical biostatistics. Lange Medical Book/ McGraw-Hill, Medical Publishing Division 3rd ed 7-9:161-218.

Lee JH, O’Keefe JH, Bell D et al (2008) Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol 52(24):1949–1956. https://doi.org/10.1016/j.jacc.2008.08.050

Verdoia M, Pergolini P, Rolla R, Sartori C, Nardin M, Schaffer A, Barbieri L, Daffara V, Marino P, Bellomo G, Suryapranata H, De Luca G (2016) Vitamin D levels and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor. Platelets 27(6):576-582

Ma L, Wang S, Chen H, Cui L, Liu X, Yang H, Li G, Liu S, Qi T, Tian H (2020) Diminished 25-OH vitamin D3 levels and vitamin D receptor variants are associated with susceptibility to type 2 diabetes with coronary artery diseases. J Clin Lab Anal 34(4):e23137. https://doi.org/10.1002/jcla.23137

Fox H, Seeger FH, Quernheim QF et al (2020) Vitamin D gene polymorphisms and risk of acute cardiovascular events, Clinical Epidemiology and Global Health. 8(4):1371–1376 https://doi.org/10.1016/j.cegh.2020.05.015

Tarighi S, Najafi M, Hossein-Nezhad A, Ghaedi H, Meshkani R, Moradi N, Fadaei R, Kazerouni F, Shanaki M (2017) Association between two common polymorphisms of vitamin D binding protein and the risk of coronary artery disease: a case-control study. J Med Biochem 36(4):349–357. https://doi.org/10.1515/jomb-2017-0015

Kavarić S, Vuksanović M, Bozović D et al (2013) Body weight and waist circumference as predictors of vitamin D deficiency in patients with type 2 diabetes and cardiovascular disease. Vojnosanit Pregl 70(2):163–169. https://doi.org/10.2298/VSP110713035K

Pilz S, Tomaschitz A, März W, Drechsler C, Ritz E, Zittermann A, Cavalier E, Pieber TR, Lappe JM, Grant WB, Holick MF, Dekker JM (2011) Vitamin D, cardiovascular disease and mortality. ClinEndocrinol (Oxf) 75(5):575–584. https://doi.org/10.1111/j.1365-2265.2011.04147.x

Judd SE, Tangpricha V (2009) Vitamin D deficiency and risk for cardiovascular disease. The American journal of the medical sciences 338(1):40–44 https://doi.org/10.1097/MAJ.0b013e3181aaee91

Orozco-Beltran D, Gil-Guillen VF, Redon J, Martin-Moreno JM, Pallares-Carratala V, Navarro-Perez J, Valls-Roca F, Sanchis-Domenech C, Fernandez-Gimenez A, Perez-Navarro A, Bertomeu-Martinez V, Bertomeu-Gonzalez V, Cordero A, Pascual de la Torre M, Trillo JL, Carratala-Munuera C, Pita-Fernandez S, Uso R, Durazo-Arvizu R, Cooper R, Sanz G, Castellano JM, Ascaso JF, Carmena R, Tellez-Plaza M, on behalf of ESCARVAL Study Group (2017) Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study. PLoSOne 12(10):e0186196. https://doi.org/10.1371/journal.pone.0186196

Laczmanski L, Milewicz A, Lwow F et al (2013) Vitamin D receptor gene polymorphism and cardiovascular risk variables in elderly Polish subjects. GynecolEndocrinol 29(3):268–272

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. Journal of Receptors and Signal Transduction 35(5):391–395. https://doi.org/10.3109/10799893.2014.959593

Schuch NJ, Garcia VC, Sandra RG et al (2013) Relationship between vitamin D receptor gene polymorphisms and the components of metabolic syndrome. Nutr J 12(96). https://doi.org/10.1186/1475-2891-12-96

Prabhakar P, Majumdar V, Kulkarni GB, Christopher R (2015) Genetic variants of vitamin D receptor and susceptibility to ischemic stroke. BiochemBiophys Res Commun 456(2):631–636. https://doi.org/10.1016/j.bbrc.2014.12.007

Zittermann A, Gummert JF, Börgermann J (2011) The role of vitamin D in dyslipidemia and cardiovascular disease. Current Pharmaceutical Design 17(9):933–942. https://doi.org/10.2174/138161211795428786

Mridula M, Ritu S (2015) Current understanding of role of vitamin D in type 2 DM. Int J Recent Sci Res 6(2):2602–2607