ASSOCIATION BETWEEN SERUM 25-HYDROXYVITAMIN D LEVELS AND VITAMIN D RECEPTOR POLYMORPHISMS IN HIV-INFECTED CHILDREN
DOI:
https://doi.org/10.22159/ijap.2019.v11s4.35288Keywords:
25-hydroxyvitamin D, HIV-infected children, VDR polymorphism, BsmI, FokIAbstract
Objective: The clinical and genetic evidence is accumulating that vitamin D may play a role in modulating human immunodeficiency virus (HIV) infection. The aim of this study was to evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in HIV-infected children and its association with vitamin D receptor (VDR) gene Bsml and Fokl polymorphisms.
Methods: Serum 25(OH)D levels were measured using 250HD Liaison XL®. The VDR genes were detected by CLART®MetaBone.
Results: This study included 34 HIV-infected children on highly active antiretroviral therapy (HAART) for more than a year, aged 6-14 y. The results revealed that the mean of serum 25(OH)D levels were 19.6±7.0 nmol/l. The mean of CD4+T-cell counts was 724 (18–1805) cell/mm3 and CD4 % was 23.72±10.77. The genotypic frequency Bsml and Fokl polymorphisms in HIV-infected children were BB 29%, Bb 41%, bb 29% and FF 47%, Ff 44%, ff 9%, respectively. Serum 25(OH)D levels were associated with Bsml polymorphisms (p<0.05), but not with Fokl polymorphisms (p>0.05).
Conclusion: The present study showed that vitamin D deficiency is common in HIV-infected children, and genetic variant could lead to altered activity of vitamin D. Therefore, it is important to consider vitamin D status routinely in preventing the development of opportunistic infections and supplementation of vitamin D is warranted among HIV-infected children on HAART.
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References
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24. Kang TJ, Jin SH, Yeum CE, Lee SB, Kim CH, Lee SH, et al. Vitamin D receptor gene taqi, bsmi and foki polymorphisms in korean patients with tuberculosis. Immune Netw 2011;11:253–7.
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29. White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun 2008;76:3837–43.
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32. Rwebembera A, Sudfeld CR, Manji KP, Duggan C, Aboud S, Fawzi WW. Prevalence and risk factors for vitamin d deficiency among tanzanian hiv-exposed uninfected infants. J Trop Pediatr 2013;59:426–9.
33. Meyzer C, Frange P, Chappuy H, Desse B, Veber F, Le Clesiau H, et al. Vitamin D deficiency and insufficiency in HIV-infected children and young adults. Pediatr Infect Dis J 2013;32:1240–4.
34. Yin M, Stein E. The effect of antiretrovirals on vitamin D. Clin Infect Dis 2011;52:406–8.
35. Aziz M, Livak B, Burke Miller J, French AL, Glesby MJ, Sharma A, et al. Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV study participants with advanced disease on HAART. Aids 2013;27:573–8.
36. Gedela K, Edwards SG, Benn P, Grant AD. Prevalence of vitamin D deficiency in HIV-positive, antiretroviral treatment-naïve patients in a single centre study. Int J STD AIDS 2014;25:488–92.
37. Topalo N, Sevilay O, S?lan F, Uluda A, Selda I, Akurut Ç. Association of vitamin d receptor gene polymorphisms in children with atopic diseases. Gene Ther Mol Biol 2014;16:55–60.
38. Eltahir Khalid K. Vitamin D receptor gene polymorphisms in Sudanese children with type 1 diabetes. AIMS Genet 2016;3:167–76.
39. Cieslinska A, Kostyra E, Chwa?a B, Moszy?ska Dumara M, Fiedorowicz E, Teodorowicz M, et al. Vitamin D receptor gene polymorphisms associated with childhood autism. Brain Sci 2017;7:115.
40. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81.
41. Gartner L, Greer F. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin d intake. Pediatrics 2003;111:908–10.
42. Food and Nutrition Board Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorous, Magnesium, Vitamin D, and Fluoride. Vol. 55, Nutrition Reviews. Washington, DC: National Academy Press; 1997. Available from: http://doi.wiley.com/ 10.1111/j.1753-4887.1997.tb01621.x. [Last accessed on 01 Jan 2019].
43. Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004 1–3. Am J Clin Nutr 2008; 88:1519–27.
44. Misra M, Pacaud D, Petryk A, Collett Solberg PF, Kappy M. Vitamin d deficiency in children and its management: a review of current knowledge and recommendations. Pediatrics 2008;122:398–417.
45. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug-metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54–8.
46. Van Den Bout Van Den Beukel CJP, Fievez L, Michels M, Sweep FCGJ, Hermus ARMM, Bosch MEW, et al. Vitamin d deficiency among HIV type 1-infected individuals in the netherlands: effects of antiretroviral therapy. AIDS Res Hum Retroviruses 2008;24:1375–82.
47. Mueller NJ, Fux CA, Ledergerber B, Elzi L, Schmid P, Dang T, et al. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated swiss HIV patients. Aids 2010;24:1127–34.
48. Hileman CO, E Turner Overton, McComsey A. Vitamin D and bone loss in HIV. 2017;11:277–84.
49. Dao CN, Patel P, Overton ET, Rhame F, Pals SL, Johnson C, et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the us general population. Clin Infect Dis 2011;52:396–405.
50. Mcnamara L, Takuva S, Chirwa T, Macphail P. Prevalence of common vitamin D receptor gene polymorphisms in HIV-infected and uninfected South Africans. Int J Mol Epidemiol Genet 2016;7:74–80.
51. Nieto G, Barber Y, Rubio MC, Rubio M, Fibla J. Association between AIDS disease progression rates and the Fok-I polymorphism of the VDR gene in a cohort of HIV-1 seropositive patients. J Steroid Biochem Mol Biol 2004;89–90:199–207.
52. de la Torre MS, Torres C, Nieto G, Vergara S, Carrero AJ, Macias J, et al. Vitamin D receptor gene haplotypes and susceptibility to HIV?1 infection in injection drug users. J Infect Dis 2008;197:405–10.
53. Barber Y, Rubio C, Fernandez E, Rubio M, Fibla J. Host genetic background at CCR5 chemokine receptor and vitamin d receptor loci and human immunodeficiency virus (HIV) type 1 disease progression among HIV?seropositive injection drug users. J Infect Dis 2001;184:1279–88.
54. Joshi L, Ponnana M, Penmetsa SR, Nallari P, Valluri V, Gaddam S. Serum vitamin D levels and VDR polymorphisms (BsmI and FokI) in patients and their household contacts susceptible to tuberculosis. Scand J Immunol 2014;79:113–9.
55. Abd-Allah SH, Pasha HF, Hagrass HA, Alghobashy AA. Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Gene 2014;536:430–4.
56. Co?kun S, Simsek S, Camkurt MA, Cim A, Celik SB. Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with an autism spectrum disorder. Gene 2016;588:109–14.
2. Van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 2011;25:671–80.
3. Huh SY, Gordon CM. Vitamin D deficiency in children and adolescents: Epidemiology, impact and treatment. Rev Endocr Metab Disord 2008;9:161–70.
4. Prentice A, Pettifor J, Nutrition SAC on, Bischoff-Ferrari H, Giovannuci E, Willett W, et al. Vitamin D deficiency: a global perspective. Nutr Rev 2008;66(10 Suppl 2):S153-64.
5. S MC, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. Am Soc Nutr Sci 2005;135:310–6.
6. Heaney RP. Serum 25-hydroxyvitamin D is a reliable indicator of vitamin D status. Am J Clin Nutr 2011;94:619–20.
7. Holick MF. High prevalence of vitamin d inadequacy and implications for health-proquest. Mayo Clin Proc 2006;81:353–73.
8. Stein SH, Tipton DA. Vitamin D and its impact on oral health--an update. J Tenn Dent Assoc 2011;91:30–5.
9. Uwitonze AM, Murererehe J, Ineza MC, Harelimana EI, Nsabimana U, Uwambaye P, et al. Effects of vitamin D status on oral health. J Steroid Biochem Mol Biol 2018;175:190–4.
10. Genco robert borgnakke wenche. Risk factors for periodontal disease. Periodontol 2013;62:59–94.
11. Grimm M, Cetindis M, Biegner T, Lehman M, Munz A, Teriete P, et al. Serum vitamin D levels of patients with oral squamous cell carcinoma (OSCC) and expression of vitamin D receptor in oral precancerous lesions and OSCC. Med Oral Patol Oral Cir Bucal 2015;20:e188–95.
12. Adeyemi OM, Weber KM, Lu Y, Cohen M. Association among vitamin D, oral candidiasis, and calprotectinemia in HIV; 2012. p. 666–70.
13. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 2014;383(9912):146–55.
14. Samuel S, Sitrin MD. Vitamin D’s role in cell proliferation and differentiation. Nutr Rev 2008;66(Suppl 2):S116-24.
15. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients 2013;5:2502–21.
16. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin d: modulator of the immune system. Curr Opin Pharmacol 2010;10:482–96.
17. Cynthia Aranow, MD Investigator. Vitamin D and the immune system. J Investig Med 2012;59:881–6.
18. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 2014;21:319–29.
19. Pike JW, Meyer MB. The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D3. Endocrinol Metab 2010;39:255–69.
20. Vaughan Shaw PG, O’Sullivan F, Farrington SM, Theodoratou E, Campbell H, Dunlop MG, et al. The impact of Vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. Br J Cancer 2017;116:1095–110.
21. Rashid MU, Muzaffar M, Khan FA, Kabisch M, Muhammad N, Faiz S, et al. Association between the bsmi polymorphism in the Vitamin D receptor gene and breast cancer risk: results from a pakistani case-control study. PLoS One 2015;10:1–16.
22. Cauci S, Maione V, Buligan C, Linussio M, Serraino D, Stinco G. BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy. Cancer Biol Med 2017;14:302.
23. Mostowska A, Lianeri M, Wudarski M, Olesinska M, Jagodzinski PP. Vitamin D receptor gene bsmi, foki, apai and taqi polymorphisms and the risk of systemic lupus erythematosus. Mol Biol Rep 2013;40:803–10.
24. Kang TJ, Jin SH, Yeum CE, Lee SB, Kim CH, Lee SH, et al. Vitamin D receptor gene taqi, bsmi and foki polymorphisms in korean patients with tuberculosis. Immune Netw 2011;11:253–7.
25. Marozik P, Mosse I, Alekna V, Rudenko E, Tamulaitiene M, Ramanau H, et al. Association between polymorphisms of VDR, COL1A1, and LCT genes and bone mineral density in belarusian women with severe postmenopausal osteoporosis. Med 2013;49:177–84.
26. Kong Y, Zheng J, Zhang W, Jiang Q, Yang X, Yu M, et al. The relationship between vitamin D receptor gene polymorphism and deciduous tooth decay in Chinese children. BMC Oral Health 2017;17:111.
27. Solanki Palak, PG. Role of vitamin D in human diseases and disorders-an overview. Pharmacologyonline 2014;4:34–42.
28. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney Int 2010;78:140–5.
29. White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun 2008;76:3837–43.
30. Kearns MD, Alvarez JA, Seidel N, Tangpricha V, Affairs V. The impact of vitamin D on infectious disease: a systematic review of controlled trials. Am J Med Sci 2016;349:245–62.
31. Mansueto P, Seidita A, Vitale G, Gangemi S, Iaria C, Cascio A. Vitamin D deficiency in HIV infection: not only a bone disorder. Biomed Res Int 2015. http://dx.doi.org/10.1155/2015/ 735615.
32. Rwebembera A, Sudfeld CR, Manji KP, Duggan C, Aboud S, Fawzi WW. Prevalence and risk factors for vitamin d deficiency among tanzanian hiv-exposed uninfected infants. J Trop Pediatr 2013;59:426–9.
33. Meyzer C, Frange P, Chappuy H, Desse B, Veber F, Le Clesiau H, et al. Vitamin D deficiency and insufficiency in HIV-infected children and young adults. Pediatr Infect Dis J 2013;32:1240–4.
34. Yin M, Stein E. The effect of antiretrovirals on vitamin D. Clin Infect Dis 2011;52:406–8.
35. Aziz M, Livak B, Burke Miller J, French AL, Glesby MJ, Sharma A, et al. Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV study participants with advanced disease on HAART. Aids 2013;27:573–8.
36. Gedela K, Edwards SG, Benn P, Grant AD. Prevalence of vitamin D deficiency in HIV-positive, antiretroviral treatment-naïve patients in a single centre study. Int J STD AIDS 2014;25:488–92.
37. Topalo N, Sevilay O, S?lan F, Uluda A, Selda I, Akurut Ç. Association of vitamin d receptor gene polymorphisms in children with atopic diseases. Gene Ther Mol Biol 2014;16:55–60.
38. Eltahir Khalid K. Vitamin D receptor gene polymorphisms in Sudanese children with type 1 diabetes. AIMS Genet 2016;3:167–76.
39. Cieslinska A, Kostyra E, Chwa?a B, Moszy?ska Dumara M, Fiedorowicz E, Teodorowicz M, et al. Vitamin D receptor gene polymorphisms associated with childhood autism. Brain Sci 2017;7:115.
40. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81.
41. Gartner L, Greer F. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin d intake. Pediatrics 2003;111:908–10.
42. Food and Nutrition Board Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorous, Magnesium, Vitamin D, and Fluoride. Vol. 55, Nutrition Reviews. Washington, DC: National Academy Press; 1997. Available from: http://doi.wiley.com/ 10.1111/j.1753-4887.1997.tb01621.x. [Last accessed on 01 Jan 2019].
43. Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004 1–3. Am J Clin Nutr 2008; 88:1519–27.
44. Misra M, Pacaud D, Petryk A, Collett Solberg PF, Kappy M. Vitamin d deficiency in children and its management: a review of current knowledge and recommendations. Pediatrics 2008;122:398–417.
45. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug-metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54–8.
46. Van Den Bout Van Den Beukel CJP, Fievez L, Michels M, Sweep FCGJ, Hermus ARMM, Bosch MEW, et al. Vitamin d deficiency among HIV type 1-infected individuals in the netherlands: effects of antiretroviral therapy. AIDS Res Hum Retroviruses 2008;24:1375–82.
47. Mueller NJ, Fux CA, Ledergerber B, Elzi L, Schmid P, Dang T, et al. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated swiss HIV patients. Aids 2010;24:1127–34.
48. Hileman CO, E Turner Overton, McComsey A. Vitamin D and bone loss in HIV. 2017;11:277–84.
49. Dao CN, Patel P, Overton ET, Rhame F, Pals SL, Johnson C, et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the us general population. Clin Infect Dis 2011;52:396–405.
50. Mcnamara L, Takuva S, Chirwa T, Macphail P. Prevalence of common vitamin D receptor gene polymorphisms in HIV-infected and uninfected South Africans. Int J Mol Epidemiol Genet 2016;7:74–80.
51. Nieto G, Barber Y, Rubio MC, Rubio M, Fibla J. Association between AIDS disease progression rates and the Fok-I polymorphism of the VDR gene in a cohort of HIV-1 seropositive patients. J Steroid Biochem Mol Biol 2004;89–90:199–207.
52. de la Torre MS, Torres C, Nieto G, Vergara S, Carrero AJ, Macias J, et al. Vitamin D receptor gene haplotypes and susceptibility to HIV?1 infection in injection drug users. J Infect Dis 2008;197:405–10.
53. Barber Y, Rubio C, Fernandez E, Rubio M, Fibla J. Host genetic background at CCR5 chemokine receptor and vitamin d receptor loci and human immunodeficiency virus (HIV) type 1 disease progression among HIV?seropositive injection drug users. J Infect Dis 2001;184:1279–88.
54. Joshi L, Ponnana M, Penmetsa SR, Nallari P, Valluri V, Gaddam S. Serum vitamin D levels and VDR polymorphisms (BsmI and FokI) in patients and their household contacts susceptible to tuberculosis. Scand J Immunol 2014;79:113–9.
55. Abd-Allah SH, Pasha HF, Hagrass HA, Alghobashy AA. Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children. Gene 2014;536:430–4.
56. Co?kun S, Simsek S, Camkurt MA, Cim A, Celik SB. Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with an autism spectrum disorder. Gene 2016;588:109–14.
Published
15-08-2019
How to Cite
SUFIAWATI, I., SAPATARINI, R., RIYANTI, E., & MAULANI, I. (2019). ASSOCIATION BETWEEN SERUM 25-HYDROXYVITAMIN D LEVELS AND VITAMIN D RECEPTOR POLYMORPHISMS IN HIV-INFECTED CHILDREN. International Journal of Applied Pharmaceutics, 11(4), 41–45. https://doi.org/10.22159/ijap.2019.v11s4.35288
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