Association between polymorphism in TaqI, BsmI, Apa1, DHCR7, GC, CYP27B1 and CYP24A1 genes and vitamin D deficiency in Saudi obese females

Main Article Content

Manal Bin obead
Sahar Abdulaziz AlSedairy
Naveed Ahmed Syed
Periasamy Vaiyapuri Subbarayan
Tahani Aljurbua
Maha Abdulaziz Aljuwayd
Shaista Arzoo
Ali Abdullah Alshatwi

Keywords

Vitamin D, obesity, SNPs, genes, BMI, Saudi., Sahar Abdulaziz AlSedairy

Abstract

Background. Obesity is an endemic disease and obese people requires larger vitamin D intakes to
achieve normal 25(OH)2D3 as compared to individuals with normal weight. This study assessed the association
of vitamin D levels with the single nucleotide polymorphism (SNPs) of genes related to obesity and vitamin D
(i.e., TaqI, BsmI, Apa1, DHCR7, GC, CYP27B1 and CYP24A1). Methods. One hundred forty two women
were involved in this study. The study tools included interview questionnaire, anthropometric measurements
(height, weight, BMI) and blood biochemical tests (glucose, insulin, cholesterol, triglyceride, HDL, LDL,
25-Hydroxyvitamin D and parathyroid assessment and SNP analysis (VDR SNPs, DHCR7, GC, CYP27B1,
CYP24A1). Results. As compared to normal vitamin D obese (NVD) subjects the weight, body mass index
(BMI) and parathyroid hormone (PTH) was significantly higher in vitamin D deficient obese (VDD) subjects.
While, total cholesterol (TC), triglyceride (TG) and vitamin D levels were significantly lower in the vitamin D
deficient group compared to the normal vitamin D group. Various variants such as TaqI, BsmI, Apa1, DHCR7,
GC rs4588 and CYP27B1 did not showed any significant association with the pathogenesis of vitamin D
deficiency related obesity. However, GC rs7041 and CYP24A1 genotypes were significantly related with vitamin
D deficiency in patients with obesity. Conclusion. This study suggests that polymorphisms in the GC and
CYP24A1 genes are related with vitamin D deficiency in obese females. These polymorphisms may become a
useful marker to predict the impending development of vitamin D deficiency in obese females. Studies have revealed that associations between genotypes of these SNPs and particular phenotypes may vary according to the following: ethnicity, interactions with environmental factors, sex, and number of participants.


 

Downloads

Download data is not yet available.
Abstract 47 | PDF Downloads 29

References

1. WHO. World Health Organization. Obesity epidemic puts millions at risk from related diseases. Press release 1997; 46:12.‏
2. Must A, Dallal GE, Dietz WH. Reference data for obesity: 85th and 95th percentiles of body mass index (wt/ht2) and triceps skinfold thickness. Am J Clin Nutr 1991; 53: 839–846.
3. Finkelstein EA, Fiebelkorn IC, Wang G. National medical spending attributable to overweight and obesity: how much, and who's paying? Health Aff (Millwood) 2003; 22 Suppl W3: 219–226.
4. World Health Organization: Health 2020: A European Policy Framework Supporting Action Across Government and Society for Health and Well-Being. Malta, WHO, 2012.  
5. NCD Risk Factor Collaboration: Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 2016; 387: 1377–1396.
6. Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism 2019; 92:6-10.
7. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes 2008; 32:1431-1437.
8. Chittawatanarat K, Pruenglampoo S, Kongsawasdi S, Chuatrakoon B, Trakulhoon V, Ungpinitpong W, Patumanond J. The variations of body mass index and body fat in adult Thai people across the age spectrum measured by bioelectrical impedance analysis. Clin Interv Aging 2011; 6: 285–294.
9. EMRO. Regional Health Systems Observatory. EMRO World Health Organization, 2006.
10. Young KA, Engelman CD, Langefeld CD, Hairston KG, Haffner SM, Bryer-Ash M, Norris JM. Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. J Clin Endocrinol Metab 2009; 94: 3306–3313.
11. Konradsen S, Ag H, Lindberg F, Hexeberg S, Jorde R. Serum 1, 25-dihydroxy vitamin D is inversely associated with body mass index. Euro J Nutr 2008; 47: 87–91.
12. Arunabh S, Pollack S, Yeh J, Aloia, JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab 2003; 88: 157–161.
13. Jones G, Strugnell SA, DeLuca HF. Current understanding of the molecular actions of vitamin D. Physiol Rev 1998; 78: 1193–1231.
14. Wong KE, Szeto FL, Zhang W, Ye H, Kong J, Zhang Z, Sun XJ, Li YC. Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins. Am J Physiol Endocrinol Metab 2009; 296: E820–E828.
15. Lin RC, Wang XL, Dalziel B, Caterson ID, Morris BJ. Association of obesity, but not diabetes or hypertension, with glucocorticoid receptor N 363 S variant. Obes Res 2003; 11: 802–808.
16. Tamura K, Suzuki M, Arakawa H, Tokuyama K, Morikawa, A. Linkage and association studies of STAT6 gene polymorphisms and allergic diseases. Int Arch Allergy and Immunol 2003; 131: 33–38.
17. Yamada Y, Ando F, Niino N, Shimokata H. Association of polymorphisms of interleukin-6, osteocalcin, and vitamin D receptor genes, alone or in combination, with bone mineral density in community-dwelling Japanese women and men. J Clin Endocrinol Metab 2003; 88: 3372–3378.
18. Holvey DN. The Merck manual of diagnosis and therapy. Merck, Sharp & Dohme Research Laboratories; 12th Edition / 1st Printing edition. 1972; pp: 1960.
19. Tietz NW. Fundamentals of clinical chemistry, Philadelphia, WB Saunders, Second edition. 1970; pp:496
20. Fossati P, Principle L. Estimation of the concentration of triglyceride in plasma and liver. Clin Chem 1982; 28:2077-2081.
21. Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499-502.
22. Phinney KW. Development of a standard reference material for vitamin D in serum. Am J Clin Nutr 2008; 88: 511S-512S.
23. Ohe MN, Santos RO, Kunii IS, Abrahão M, Cervantes O, Carvalho AB, Vieira JGH. Usefulness of intraoperative PTH measurement in primary and secondary hyperparathyroidism: experience with 109 patients. Arq Bras Endocrinol Metabol 2006; 50: 869-875.
24. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008; 87: 1080S-1086S.
25. Christie FT, Mason L. Knowledge, attitude and practice regarding vitamin D deficiency among female students in Saudi Arabia: a qualitative exploration. Int J Rheum Dis 2011; 14: 22-29.
26. Pilz S, Grübler M, Gaksch M, Schwetz V, Trummer C, Hartaigh BÓ, Verheyen N, Tomaschitz A, März W. Vitamin D and Mortality. Anticancer Res 2016: 36:1379–1387.
27. Al-Turki HA, Sadat-Ali M, Al-Elq AH, Al-Mulhim FA, Al-Ali AK. 25-Hydoxyvitamin D levels among healthy Saudi Arabian women. Saudi Med J 2008; 29: 1765–1768.
28. Ardawi M-S, Qari M, Rouzi A, Maimani A, Raddadi R. Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre-and postmenopausal women. Osteoporos Int 2011; 22: 463–475.
29. Ardawi M-S, Sibiany A, Bakhsh T, Qari M, Maimani A. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int 2012; 23: 675–686.
30. Alzaheb RA, Al-Amer O. Prevalence and predictors of hypovitaminosis D among female university students in Tabuk, Saudi Arabia. Clin Med Insights Women’s Health 2017; 10: 1179562X17702391.
31. World Health Organization. Non communicable diseases country profiles 2011 WHO global report, 2011.
32. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000; 72:690–693.
33. Ramiro-Lozano JM, Calvo-Romero JM. Effects on lipid profile of supplementation with vitamin D in type 2 diabetic patients with vitamin D deficiency. Ther Adv Endocrinol Metab 2015; 6: 245–248.
34. Botella-Carretero JI, Alvarez-Blasco F, Villafruela JJ, Balsa JA, Vázquez C, Escobar-Morreale HF. Vitamin D deficiency is associated with the metabolic syndrome in morbid obesity. Clin Nutr 2007; 26: 573–580.
35. Steger FL. Associations between vitamin D status and blood lipid parameters in healthy, older adults. Iowa State University Capstones, Graduate Theses and Dissertations. 2013; 1-85.
36. Ishida H, Norman AW. Demonstration of a high affinity receptor for 1, 25-dihydroxyvitamin D3 in rat pancreas. Mol Cell Endocrinol 1988; 60:109-117.
37. Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE, Hewison M. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol 2004; 89-90:121-125.
38. Heaney RP. Toward a physiological referent for the vitamin D requirement. J Endocrinol Invest 2014; 37: 1127–1130.
39. Steingrimsdottir L, Gunnarsson O, Indridason OS, Franzson L, Sigurdsson G. Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. JAMA 2005; 294: 2336–2341.
40. Adami S, Viapiana O, Gatti D, Idolazzi L, Rossini M. Relationship between serum parathyroid hormone, vitamin D sufficiency, age, and calcium intake. Bone 2008; 42: 267–270.
41. Oelzner P, Müller A, Deschner F, Hüller M, Abendroth K, Hein G, Stein G. Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tissue Int 1998; 62: 193–198.
42. Jorde R, Sneve M, Emaus N, Figenschau Y and Grimnes G. Cross-sectional and longitudinal relation between serum 25-hydroxyvitamin D and body mass index: the Tromsø study. Eur J Nutr 2010; 49: 401–407.
43. Al-Elq AH, Sadat-Ali M, Al-Turki HA, Al-Mulhim FA, Al-Ali AK. Is there a relationship between body mass index and serum vitamin D levels? Saudi Med J 2009; 30: 1542–1546.
44. Stein EM, Laing EM, Hall DB, Hausman DB, Kimlin MG, Johnson MA, et al. Serum 25-hydroxyvitamin D concentrations in girls aged 4–8 y living in the southeastern United States. Am J Clin Nutr 2006; 83: 75–81.
45. Rankinen T, Kim SY, Pérusse L, Després JP, Bouchard C. The prediction of abdominal visceral fat level from body composition and anthropometry: ROC analysis. Int J Obes Relat Metab Disord 1999; 23:801‑809.
46. Fung GJ, Steffen LM, Zhou X, Harnack L, Tang W, Lutsey PL et al. Vitamin D intake is inversely related to risk of developing metabolic syndrome in African American and white men and women over 20 y: the coronary artery risk development in young adults study. Am J Clin Nutr 2012; 96: 24–29.
47. Jenster G, Spencer TE, Burcin MM, Tsai SY, Tsai MJ, and O’Malley BW. Steroid receptor induction of gene transcription: a two-step model. Proc Natl Acad Sci USA 1997; 94: 7879–84.
48. 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: 726–76.
49. Ferreira F, Duarte JA. Accuracy of Body Mass Index, Waist Circumference and Body Surface Index to Diagnose Overweight and Obesity in Adolescents. Arch Exercise Health Dis 2013; 4: 299–306.
50. Signorello LB, Shi J, Cai Q, Zheng W, Williams SM, Long J, Cohen SS, Li G, Hollis BW, Smith JR, Blot WJ. Common variation in vitamin D pathway genes predicts circulating 25-hydroxyvitamin D levels among African Americans. PloS One 2011; 6: e28623.
51. Nissen J, Rasmussen LB, Ravn-Haren G, Andersen EW, Hansen B, Andersen R, Mejborn H, Madsen KH, Vogel U. Common variants in CYP2R1 and GC genes predict vitamin D concentrations in healthy Danish children and adults. PloS One 2014; 9: e89907
52. Santos BR, Mascarenhas LP, Satler F, Boguszewski MC and Spritzer PM. Vitamin D deficiency in girls from South Brazil: a cross-sectional study on prevalence and association with vitamin D receptor gene variants. BMC Pediatrics 2012; 12: 62.
53. Bikle DD. Vitamin D: role in skin and hair. In: Feldman D., Pike J.W., Glorieux F.H., editors. Vitamin D. Elsevier Academic Press; Boston, MA: 2005; pp. 609–630.
54. Cooke NE, Haddad JG. Vitamin D binding protein (Gcglobulin). Endocr Rev 1989; 10: 294–307.
55. Nimitphong H, Saetung S, Chanprasertyotin S, Chailurkit LO, Ongphiphadhanakul B. Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D3 or D2 supplementation. Nutr J 2013; 12: 39.
56. Nissen J, Vogel U, Ravn-Haren G, Andersen EW, Madsen KH, Nexø BA, and Rasmussen LB. Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D3–fortified bread and milk during winter in Denmark. Am J Clin Nutr 2015; 101: 218-227.
57. Robien K, Butler LM, Wang R, Beckman KB, Walek D, Koh WP, Yuan JM. Genetic and environmental predictors of serum 25-hydroxyvitamin D concentrations among middle-aged and elderly Chinese in Singapore. Br J Nutr 2013; 109: 493–502.
58. Xu X, Mao J, Zhang M, Liu H, Li H, Lei H and Gao M. Vitamin D deficiency in Uygurs and Kazaks is associated with polymorphisms in CYP2R1 and DHCR7/NADSYN1 genes. Med Sci Monit 2015; 21:1960-1968.
59. Batai K, Murphy AB, Shah E, Ruden M, Newsome J, Agate S, Dixon MA, Chen HY, Deane LA, Hollowell CM, Ahaghotu C, Kittles RA. Common vitamin D pathway gene variants reveal contrasting effects on serum vitamin D levels in African Americans and European Americans. Hum Genet 2014; 133: 1395–1405.
60. Zhang MC, Li HX, Liu HM, Lei H, Han L, Gao M, Mao JF, Xu XJ. Serum vitamin D is low and inversely as¬sociated with LDL cholesterol in the Kazak ethnic population: a cross-sec¬tional study. Med Sci Monit 2014; 20: 1274–1283.
61. Elkum N, Alkayal F, Noronha F, Ali MM, Melhem M, Al-Arouj, Bennakhi A, Alsmadi O, Abubaker J. Vitamin D insufficiency in Arabs and South Asians positively associates with polymorphisms in GC and CYP2R1 genes. PLoS One 2014; 9: e113102.
62. Basit, S. Vitamin D in health and disease: a literature review. Br J Biomed Sci 2013; 70: 161-172.
63. Panda DK, Miao D, Tremblay ML, Sirois J, Farookhi R, Hendy GN, et al. Targeted ablation of the 25-hydroxyvitamin D 1alpha-hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc Natl Acad Sci USA 2001; 98: 7498–7503.
64. Omdahl JL, Bobrovnikova EA, Choe S, Dwivedi PP, and May BK. Overview of regulatory cytochrome P450 enzymes of the vitamin D pathway. Steroids 2001; 66: 381–389.