Association between Vitamin D Receptor methylation with vitamin D, parathyroid hormone levels and lipid profile in normal and obese Saudi Females
Main Article Content
Keywords
VDR (vitamin D receptor); BMI; CpG methylation; PTH.
Abstract
Obesity has been encountered as one of the most common disorder with major public health implications. Various epidemiologic, genetic and metabolic data have shown significant role of vitamin D in obesity. The purpose of this study was to determine the connotation between VDR methylation at three sites and various variables such as weight, height, BMI, waist circumference, lipids profile (TG, HDL-C, LDL-C and total cholesterol), vitamin D, and PTH in normal and obese Saudi females. For this purpose; 100 Saudi females (31 normal weight with BMI<25 and 69 obese with BMI>30) with no chronic diagnosed diseases aged from 18 to 60 years were evaluated. Spearman rank correlation coefficient (R) with graphic representations using linear regression has been used to find the correlation between various variables. In studying the VDR methylation correlations with different variables, the results showed that; methylation of VDR at site 1 showed positive non-significant correlation with weight, BMI, serum TG and LDL levels in addition to serum vitamin D level. On the other hand, there was negative correlation with TC, HDL and PTH (parathyroid hormone). These results indicated that; methylation at site 1 could decrease PTH, HDL & TC levels. Furthermore, methylation of VDR at both site 2 and site 3 showed positive non-significant correlations with TC, TG, LDL levels in addition to serum levels of vitamin D and PTH. While it showed a negative correlation with only HDL level. Methylation of VDR at site 2 and 3 is related with obesity, it was significantly correlated with weight, BMI and waist circumference.
References
2. Nan C, Guo B, Warner C, Fowler T, Barrett T, Boomsma D, Nelson T, Whitfield K, Beunen G, Thomis M, Maes H, Derom C, Ordon J, Deeks J, Zeegers M. Heritability of body mass index in pre-adolescence, young adulthood and late adulthood. Eur J Epidemiol 2012; 27:247–253.
3. Habib SS. Body mass index and body fat percentage in assessment of obesity prevalence in Saudi adults. Biomed Environ Sci 2013; 26: 94–9.
4. Lazarevich I, Irigoyen-Camacho ME, Velazquez-Alva Mdel C. Obesity, eating behavior and mental health among university students in Mexico City. Nutr Hosp 2013; 28: 1892-9.
5. Parikh SJ, Edelman M, Uwaifo GI, Freedman RJ, Semega-Janneh M, Reynolds J, Yanovski JA. The relationship between obesity and serum 1, 25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab 2004; 89: 1196–9.
6. Al-Hazmi AS. Relation of vitamin D with bone mineral density and bone turnover markers in healthy Saudi men. International Journal of Advanced Research 2016; 4: 205-11.
7. Vimeswaran KS, Berry DJ, Lu C, et al. Causal relationship between obesity and vitamin D status: Bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med 2013; 10: 1549–676.
8. Carlberg C, Seuter S, Heikkinen S. The first genome wide view of vitamin D receptor locations and their mechanistic implications, Anticancer Research 2012; 32:271–282.
9. Pike JW, Meyer MB, Bishop KA. Regulation of target gene expression by the vitamin D receptor—an update on mechanisms. Reviews in Endocrine and Metabolic Disorders 2012; 13: 45–55.
10. Wong KE, Kong J, Zhang W, Szeto FL, Ye H, Deb DK, Brady MJ, Li YC. Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice. J Biol Chem 2011; 286: 33804–33810.
11. Ochs-Balcom H, Chennamaneni R, Millen A, Shields P, Marian C. Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes. Am J Clin Nutr 2011; 93: 5-10.
12. Dejeux E, El Abdalaoui H, Gut IG, Tost J. Identification and Quantification of Differentially Methylated Loci by the Pyrosequencing™ Technology. DNA Methylation;Methods in Molecular Biology 2009; 507:189-205.
13. Houde AA, Légaré C, Biron S, Lescelleur O, Biertho L, Marceau S, Tchernof A, Vohl AC, Hivert MF, Bouchard L. Leptin and adiponectin DNA methylation levels in adipose tissues and blood cells are associated with BMI, waist girth and LDL-cholesterol levels in severely obese men and women. BMC medical genetics 2015; 16: 29.
14. Dubois L, Ohm Kyvik K, Girard M, Tatone-Tokuda F, Perusse D, Hjelmborg J, Skytthe A, Rasmussen F, Wright MJ, Lichtenstein P, Martin NG. Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: an international study of over 12,000 twin pairs. PLoS One 2012; 7:e30153.
15. Yao Y, He L, Duan Y, Liang W, Nie Z, Jin Y, Wu X, Fang Y. A meta-analysis of the relationship between vitamin D deficiency and obesity. Int J Clin Exp Med 2015; 8: 14977-84.
16. Lee S, Clark S, Gill R, Christakos S. 1,25-Dihydroxyvitamin D3 and pancreatic b-cell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology 1994; 134: 1602-10.
17. Afzal S, Brondum-Jacobsen P, Bojesen S, Nordestgaard B. Vitamin D concentration obesity and risk of diabetes: a Mendelian randomization study. Lancet Diabetes Endocrinology 2014; 2: 298-306.
18. Kull M, Kallikorm R, Lember M. Body mass index determines sunbathing habits: Implications on vitamin D levels. Intern Med J 2009; 39: 256–8.
19. Blum M, Dolnikowski G, Seyoum E, et al. Vitamin D3 in fat tissue. Endocrinology 2008; 33: 90–4.
20. Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ, Evans SRT. 1, 25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition. Cancer Research 1993; 53: 3712–3718.
21. Buras RR, Schumaker LM, Davoodi F, Brenner RV, Shabahang M, Nauta RJ, Evans SR. Vitamin D receptors in breast cancer cells. Breast Cancer Research and Treatment 1994: 31:191–202.
22. Anderson MG, Nakane M, Ruan X, Kroeger PE, Wu-Wong JR. Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemotherapy and Pharmacology 2006; 57: 234–240.
23. Ye WZ, Reis AF, Dubois-Laforgue D, Bellanné-Chantelot C, Timsit J, Velho G. Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol 2001; 145: 181-6.
24. Ács O, Péterfia B, Hollósi P, Luczay A, Török D, Szabó A: Methylation Status of CYP27B1 and IGF2 Correlate to BMI SDS in Children with Obesity. Obes Facts 2017; 10:353-362.
25. Wang R, Keisala T, Solakivi T, Minasyana A, Kalueff AV, Tuohimaa P. Serum cholesterol and expression of ApoAI, LXRβ and SREBP2 in vitamin D receptor knock-out mice. Journal of Steroid Biochemistry and Molecular Biology 2009; 113: 222–226.
26. Jorde R, Grimnes G. Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids. Prog Lipid Res 2011; 50:303-12.
27. Holick MF. Vitamin D status: measurement, interpretation and clinical application. Ann Epidemiol 2009; 19: 73-8.
28. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004; 80: 1689-96.
29. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, S Vasan R. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117:503-11.