Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study.

By R. Wilkinson, Martin Llewelyn, Z. Toossi, P. Patel, G. Pasvol, A. Lalvani, Dennis J Wright, Mohammed Latif, R. Davidson. The Lancet, 2000

793 citations recorded by the source corpus.

BACKGROUND Susceptibility to disease after infection by Mycobacterium tuberculosis is influenced by environmental and host genetic factors. Vitamin D metabolism leads to activation of macrophages and restricts the intracellular growth of M. tuberculosis. This effect may be influenced by polymorphisms at three sites in the vitamin D receptor (VDR) gene. We investigated the interaction between serum vitamin D (25-hydroxycholecalciferol) concentrations and VDR genotype on susceptibility to tuberculosis. METHODS This study was a hospital-based case-control analysis of Asians of Gujarati origin, a mainly vegetarian immigrant population with a high rate of tuberculosis. We typed three VDR polymorphisms (defined by the presence of restriction endonuclease sites for Taq1, Bsm1, and Fok1) in 91 of 126 untreated patients with tuberculosis and 116 healthy contacts who had been sensitised to tuberculosis. Serum 25-hydroxycholecalciferol was recorded in 42 contacts and 103 patients. FINDINGS 25-hydroxycholecalciferol deficiency was associated with active tuberculosis (odds ratio 2.9 [95% CI 1.3-6.5], p=0.008), and undetectable serum 25-hydroxycholecalciferol (<7 nmol/L) carried a higher risk of tuberculosis (9.9 [1.3-76.2], p=0.009). Although there was no significant independent association between VDR genotype and tuberculosis, the combination of genotype TT/Tt and 25-hydroxycholecalciferol deficiency was associated with disease (2.8 [1.2-6.5]) and the presence of genotype ff or undetectable serum 25-hydroxycholecalciferol was strongly associated with disease (5.1 [1.4-18.4]). INTERPRETATION 25-hydroxycholecalciferol deficiency may contribute to the high occurrence of tuberculosis in this population. Polymorphisms in the VDR gene also contribute to susceptibility when considered in combination with 25-hydroxycholecalciferol deficiency.

Subfields: Emergency Medicine, Infectious Diseases, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/932e7b0475a569a9834e1329076a195de4b6595b

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In Pathology and Forensic Medicine

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Citations in the corpus

• Demographic Differences and Trends of Vitamin D Insufficiency in the US Population, 1988–2004 (2009, neutral): “Mexican American 5305 11 6 (5-7) 3211 18 8 (6-11)”
• Vitamin D in preventive medicine: are we ignoring the evidence? (2003, background): “It has recently been demonstrated that the VDR genotype at the Taq1 restriction site influences susceptibility to tuberculosis indicating a role of vitamin D in the pathogenesis of the disease (Wilkinson et al. 2000).”
• Innate Immunity to Mycobacterium tuberculosis (2002, background): “tween tuberculosis and functional gene polymorphism for various macrophage products (18, 19, 247, 248).”
• Respiratory Epithelial Cells Convert Inactive Vitamin D to its Active Form (2008, background): “tuberculosis infection and often have a more severe course of disease (20,21).”
• The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. (2012, background): “(208) pooled data from prospective observational studies and demonstrated an overall association of 25(OH)D baseline levels in the lowest compared with the highest 25(OH)D categories defined in each study.”