Serum vitamin D and vitamin D receptor gene FokI polymorphisms in children with tuberculosis

  • Ariesta Karmila Department of Child Health, Sriwijaya University Medical School, Palembang, Indonesia.
  • Muhammad Nazir Department of Child Health, Sriwijaya University Medical School, Palembang, Indonesia.
  • Kiagus Yangtjik Department of Child Health, Sriwijaya University Medical School, Palembang, Indonesia.
  • Yuwono Yuwono Department of Microbiology, Sriwijaya University Medical School, Palembang, Indonesia.
Keywords: vitamin D deficiency, VDR FokI polymorphism, tuberculosis, children

Abstract

Background Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are strongly associated with tuberculosis (TB) susceptibility in countries with four seasons. As a country with sufficient sunlight for vitamin D production in skin, the incidence of TB in Indonesia remains high. Objective To assess for possible associations between the incidence of tuberculosis and serum vitamin D level, as well as VDR FokI polymorphisms in children. Methods A case-control study was conducted at the Department of Child Health, Dr. Mohammad Hoesin Hospital, Palembang from November 2011 to April 2012. Subjects were children with TB (the case) and children without TB who had been exposed to TB in the home (the control). Serum vitamin D [1,25(OH)2D3 or calcitriol] level was measured by immunodiagnostic system (IDS) 1,25-dihydroxy vitamin D enzyme immunoassay (EIA) kit. The VDR FokI polymorphisms were identified by polymerase chain reaction (PCR) and restriction-fragment length polymorphism (RFLP) analysis. Results Sixty subjects was divided equally into the case and control groups. The mean serum calcitriol level in the case group was significantly lower than that of the control group [105.5 (SD 66.9) pmol/L vs. 162.9 (SD 52.9) pmol/L, respectively; (P=0.001)]. We found 9 subjects with calcitriol deficiency, 8 in the TB group and 1 in the healthy contact group (OR 10.5; 95%CI 1.2 to 90.7) The VDR FokI polymorphism was seen in 28 subjects in the case group and 22 in the control group (OR 5.0; 95%CI 0.9 to 26.4). Conclusion Vitamin D (calcitriol) deficiency and lower serum levels are associated with higher risk of TB in children. The VDR gene FokI polymorphism also contributes to susceptibility for TB.

References

Chocano-Bedoya P, Ronnenberg AG. Vitamin D and tuberculosis. Nutr Rev. 2009;67:289-93.

Gao L, Tao Y, Zhang L, Jin Q. Vitamin D receptor genetic polymorphisms and tuberculosis: updated systematic review and meta-analysis. Int J Tuberc Lung Dis. 2010;14:15–23.

Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008;37:113-9.

Direktorat Jenderal Pengendalian Penyakit & Penyehatan Lingkungan. Kementerian Kesehatan Republik Indonesia. Pedoman nasional pengendalian tuberculosis. Jakarta: Kementerian Kesehatan Indonesia; 2011. p.6.

Chesney RW, Hamstra AJ, DeLuca HF. Rickets of prematurity. Supranormal levels of serum 1,25 dihydroxyvitamin D. Am J Dis Child. 1981;135:34-7.

Walsh PS, Metzger DA, Higuchi R. Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques. 1991;10:506-13.

Davies PD, Grange JM. Factors affecting susceptibility and resistance to tuberculosis. Thorax. 2001;56:23-9.

Gartner LM, Greer FR, Section on Breastfeeding and Committee on Nutrition. American Academy of Pediatrics. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics. 2003;111:908-10.

Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338:143-56.

Talat N, Perry S, Parsonnet J, Dawood G, Hussain R. Vitamin D deficiency and tuberculosis progression. Emerg Infect Dis. 2010;16:853-5.

Sasidharan PK, Rajeev E, Vijayakumari V. Tuberculosis and vitamin D deficiency. J Assoc Physicians India. 2002;50:554–8.

Gibney KB, MacGregor L, Leder K, Torresi J, Marshall C, Ebeling PR, et al. Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin Infect Dis. 2008;46:443-6.

Ustianowski A, Shaffer R, Collin S, Wilkinson RJ, Davidson RN. Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London. J Infect. 2005;50:432-7.

Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet. 2000;355:618-21.

Syafii AZ, Sukadi A, Setiabudiawan B. Association between serum vitamin D level and tuberculosis in children. Paediatr Indones. 2008;48:350-3.

Grange JM, Davies PD, Brown RC, Woodhead JS, Kardjito T. A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle. 1985;66:187–91.

Selvaraj P, Kurian SM, Chandra G, Reetha AM, Charles N, Narayanan PR. Vitamin D receptor gene variants of BsmI, ApaI, TaqI, and FokI polymorphisms in spinal tuberculosis. Clin Genet. 2004;65:73-6.

Liu W, Cao WC, Zhang CY, Tian L, Wu XM, Habbema JD, et al. VDR and NRAMP1 gene polymorphisms in susceptibility to pulmonary tuberculosis among the Chinese Han population: a case-control study. Int J Tuberc Lung Dis. 2004;8:428-34.

Setiabudiawan B, Kartasasmita CB, Garna H, Parwati I, Maskoen AM. Polimorfisme FokI, BsmI, ApaI, dan TaqI gen reseptor vitamin D pada kejadian tuberkulosis anak. MKB. 2010;42:187-94.

Wilbur AK, Kubatko LS, Hurtado AM, Hill KR, Stone AC. Vitamin D receptor gene polymorphisms and susceptibility M. tuberculosis in native Paraguayans. Tuberculosis. 2007;87:329-37.

Published
2015-10-01
How to Cite
1.
Karmila A, Nazir M, Yangtjik K, Yuwono Y. Serum vitamin D and vitamin D receptor gene FokI polymorphisms in children with tuberculosis. PI [Internet]. 1Oct.2015 [cited 19Apr.2024];55(5):263-. Available from: https://www.paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/47
Received 2016-02-01
Published 2015-10-01