Association of Vitamin D Receptor Gene Polymorphism with Metabolic Syndrome and Type 2 Diabetes Mellitus in a Sample of Egyptian Patients Submitted: Sep 28, 2018 Accepted: Dec 29, 2018 Published online: 18 Sept, 2019

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Amany Ragab Youssef Mohamed El-Dosoky Mohamed El-Shafey Sally Abed

Abstract

Background. There are insufficient data on the association of vitamin D receptor (VDR) genes polymorphism and type 2 diabetes mellitus (type 2 DM), and various components of metabolic syndrome among Egyptian patients. The aim of the present study was to study the association of different SNPs of VDR genes  BsmI, ApaI, TaqI and FokI and components of metabolic syndrome and type 2 DM among cohort of Egyptian patients. Methods. The study is a case-control study. Patients included in the study were divided into three groups. Group 1 included 78 patients with type 2 DM; group 2 included 72 patients with metabolic syndrome and one hundred age-matched healthy subjects were served as control group. Full biochemical study and serum 25 hydroxy vitamin D (25(OH)D) were done. Purified DNA was subjected to study with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for genotyping of SNPs of VDR gene. Data were presented as mean and standard deviation, and were analysed as appropriate by using the one-way ANOVA or paired t-test. Pearson correlation coefficient was used to correlate between variables. Results. Study of VDR genetic polymorphism had shown significant increase in the prevalence of Ff genotypes among diabetic patients and patients with manifestations of metabolic syndrome. There was significant negative correlation between 25(OH)D and total cholesterol, triglyceride, fasting and post-prandial blood glucose levels, waist circumference and diastolic blood pressure. Conclusion. The genetic polymorphism of VDR might play a role in the pathophysiology of type 2 DM and metabolic syndrome., however, more longitudinal studies are still required to support these finding.

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Keywords

Metabolic syndrome, Diabetes mellitus, Polymorphism, Vitamin D receptor

How to Cite
Youssef , A. R., El-Dosoky , M., El-Shafey , M., & Abed , S. (2019). Association of Vitamin D Receptor Gene Polymorphism with Metabolic Syndrome and Type 2 Diabetes Mellitus in a Sample of Egyptian Patients. Advances in Medicine and Medical Research, 2(1), 1-8. https://doi.org/10.31377/ammr.v2i1.594
Section
Original Articles
Author Biography

Amany Ragab Youssef , Clinical Pathology Department, Mansoura University Faculty of Medicine, Mansoura 35516, Egypt.

Amany Ragab Youssef, Clinical Pathology Department, Mansoura University Faculty of Medicine, Mansoura 35516, Egypt

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Corresponding Author:

Email: amanyragab2015@gmail.com

Tel: 00201119561822

References

International Diabetes Federation (IDF), 2011. Diabetes atlas global burden, epidemiology and morbidity. Diabetes and impaired glucose tolerance. Available online: http://www.diabetesaltas.org/content/diabetes-and impaired-glucose-tolerance.

Melamed ML, Michos ED, Post W. et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Inteen Med. 2008; 168:629–637.

Palomer X, Gonzalez-Clemente JM, Blanco-Vaca F et al. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus:.Diabetes Obes Metab. 2008; 10:185–197

Pittas AG, Sun Q, Manson JE, et al. Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in women. Diabetes Care. 2010; 33: 2021–2023.

Strange RC, Shipman KE, Ramachandran S. Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes. 2015 10; 6(7): 896-911.

Al-Daghri NM, Alkharfy KM, Al-Saleh Y et al .Modest reversalof metabolic syndrome manifestations with vitamin D status correction: a 12-month prospective study. Metabolism. 2012; 61:661–666.

Alkharfy KM, Al-Daghri NM, Al-Attas OS, et al. Variants of endothelial nitric oxidesynthase gene are associated with components of metabolic syndrome in an Arabpopulation. Endocrine J. 2012; 59:253–263.

Trayhurn P, O'Hara A, Bing C. Interrogation of microarray datasets indicates that macrophagesecreted factorsstimulate the expression of genes associated with Vitamin D metabolism (VDR and CYP27B1) in human adipocytes. Adipobiology. 2011; 3:2934.

Ching S, Kashinkunti S, Niehaus MD et al. Mammary adipocytes bioactivate 25hydroxyvitaminD3 andsignal via Vitamin D3 receptor, modulating mammary epithelial cell growth. J Cell Biochem. 2011; 112:3393405.

Ding C, Wilding JP, Bing C. 1,25 dihydroxyvitaminD3 protects against macrophage induced activation of NFkBand MAPK signalling and chemokine release in human adipocytes. PLoS One. 2013; 8:e61707.

Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006; 92: 4–8.

Uitterlinden AG, Fang Y, van Meurs JB ,et al. Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. J Steroid Biochem Mol Biol. 2004; 89–90:187–193.

Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006; 371:1–12.

Bid HK, Konwar R, Aggarwal CG, et al. Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetesmellitus: a North Indian study. Ind J Med Sci. 2009; 63:187–194.

Filus A, Trzmiel A, Kuliczkowska-Plaksej J, et al. Relationship between vitamin D receptor Bsm1 and FokI polymorphismsand anthropometric and biochemical parameters describing metabolic syndrome. The Aging Male. 2008; 11:134–139.16. Mostowska A, Lianeri M, Wudarski M, Olesinska M, Jagodzinski PP. Vitamin D receptor gene Bsm1, FokI, Apa1 and Taq1 polymorphisms and the risk of systemic lupus erythmatosus. Mol Biol Rep. 2013; 40:803-810.

Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP .Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004; 338:143–156.

Arai H, Miyamoto K-I, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E.A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japan women. J Bone Miner Res. 1997; 12:915–921 1.

World Health Organization, Definition and Diagnosis of Diabetes Mellitus and Intermediate. Hyperglycemia. 2006; 30 (2):263–269.

Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112:2735–2752.

Abdeltif E, Benrahma H , Charoute H, et al. Vitamin D receptor gene polymorphisms and vitamin D status and susceptibility to type 2 diabetes mellitus in Moroccans patients . Int J Sci Res Pub. 2014; 8:23-28.

Riggs BL, Nguyen TV, Melton LJ, et al. The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women. J Bone Miner Res. 1995; 10:991-6.

Oh JY and Barrett-Connor E. Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the Rancho Bernardo Study. Metabolism. 2002; 51:356–359.

Cantorna MT. Mechanisms underlying the effect of vitamin D on the immune system. Proc Nutr Soc. 2010; 69:286–289.

Schuch NJ, Garcia VC, Sandra RG, et al. Relationship between vitamin D receptor gene polymorphisms and the components of metabolic syndrome. Nutr J. 2013; 12;96.

Li L, Wu B, Liu JY, et al. Vitamin D Receptor Gene Polymorphisms and Type 2 Diabetes: A Meta-analysis. Arch Med Res. 2013;235-241.

Neyestani TR, Djazayery A, Shab-Bidar S, et al. Vitamin D Receptor Fok-I polymorphism modulates diabetic host response tovitamin D intake: need for a nutrigenetic approach. Diabetes Care. 2013; 36:550–556.

Mackawy AMH, Badawi MEH. Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients. Meta Gene 2. 2014;540–556.

Malecki MT, Frey J, Moczulski D, et al. VDR gene polymorphisms and association with type 2 diabetes mellitus in a Polish population. Exp Clin Endocrinol Diabetes. 2003; 111:505–509.

Nosratabadi R, Arababadi MK, Salehabad VA, et al. Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type-2 diabetes. Int J Immunogen. 2010; 37:493–497.

Speer G, Cseh K, Winkler G, et al. Oestrogen and vitamin D receptor (VDR) genotypes and the expression of ErbB-2 and EGF receptor in human rectal cancers. Eur J Cancer. 2001; 37:1463–1468.

Ye WZ, Reis AF, Dubois-Laforgue D, et al. Vitamin D receptor gene polymorphisms are associatedwith obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol. 2001; 145:181–186.

Zemel MB, Shi H, Greer B, et al. Regulation of adiposity by dietary calcium. FASEB J. 2000; 14:1132–1138.

Cho HJ, Kang HC, Choi SA. The possible role of Ca2+ on the 8 Vit D receptor polymorphism in type 2 DM and metabolic syndrome activation of microsomal triglyceride transfer protein in rat hepatocytes. Biol Pharm Bull. 2005;28 (8): 1418–1423

Kamycheva E, Jorde R, Figenschau Y, et al. Insulin sensitivity in subjects with secondary hyperparathyroidism and the effect of a low serum 25-hydroxyvitamin D level on insulin sensitivity. J Endocrinol Invest. 2007; 30:126–132.

Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998; 15: 539-553.

Einhorn D, Reaven GM, Cobin RH, et al. American College of Endocrinology position statementon the insulin resistance syndrome. Endocr Pract. 2003; 9:237-252.

Gagnon C, Lu ZX, Magliano DJ, et al. Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab. J Clin Endocrinol Metab. 2012; 97:1953-1961.

Parker J, Hashmi O, Dutton D, et al. Levels of vitamin D and cardio-metabolic disorders: systematic review and meta-analysis. Maturitas. 2010; 65:225-236.

Alberti KG, Zimmet P and Shaw J. The metabolic syndrome - a new worldwide definition. Lancet. 2005; 366: 1059-1062.

Zimmet P, Alberti KG, Serrano R?os M. A New International Diabetes Federation Worldwide Definition of the Metabolic Syndrome: the Rationale and the Results. Revista Espa?ola de Cardiolog?a. 2005; 58: 1371-1375.

Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009; 120: 1640-1645.

Zimmet P, Alberti KG, Kaufman F, et al. The metabolic syndromein children and adolescents - an IDF consensus report. Pediatr Diabetes. 2007; 8:299-306.

Wang H, Chen W, Dongqing Li D, Yin X et al. Vitamin D and Chronic Diseases. Aging Dis. 2017; 8: 346-353.

Kull M, Kallikorm R, Lember M. Body mass index determines sunbathing habits: implications on vitamin D levels. Int Med J. 2009; 39:256-258.

Harris SS and Dawson-Hughes B. Reduced sun exposure does not explain the inverse association of 25-hydroxyvitamin D with percent body fat in older adults. J Clin Endocrinol Metab. 2007; 92:3155-3157.

Strange RC, Shipman KE, Ramachandran S. Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes. 2015; 6(7):896-911.

Kim DH, Sabour S, Sagar UN,et al. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol. 2008; 102:1540–1544.

Wang JH, Keisala T, Solakivi T, et al. Serum cholesterol and expression of ApoAI, LXR beta and SREBP2 in vitamin D receptor knock-out mice. J Steroid Biochem Mol Biol. 2009; 113:222–226.

Kadowaki S and Norman AW. Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas. J Clin Invest. 1984; 73:759–766.

Bourlon PM, Faure-Dussert A, Billaudel B, et al. Relationship between calbindin-D28K levels in the A and B cells of the rat endocrine pancreas and the secretion of insulin and glucagon: influence of vitamin D3 deficiency and 1,25-dihydroxyvitamin

D3. J Endocrinol. 1996; 148:223–232.52. Bourlon PM, Billaudel B and Faure-Dussert A. Influence of vitamin D3 deficiency and 1,25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the at endocrine pancreas. J Endocrinol. 1999; 160:87–95.