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Vdr tuberculosis

Ester L Acen, William Worodria, Peter Mulamba, Andrew Kambugu, Joseph Erume
Background:Mycobacterium tuberculosis (TB) is still a major problem globally and especially in Africa. Vitamin D deficiency has been linked to TB in the past and studies have found vitamin D deficiency to be common among Ugandan TB patients. The functional activity of vitamin D is dependent on the genotype of the vitamin D receptor (VDR) polymorphic genes. Recent findings have indicated that VDR polymorphisms may cause increased resistance or susceptibility to TB. The vitamin D ligand and its receptor play a pivotal role in innate immunity by eliciting antimicrobial activity, which is important in prevention of TB...
2016: F1000Research
Yan Cao, Xinjing Wang, Zhihong Cao, Xiaoxing Cheng
INTRODUCTION: The association between FokI polymorphism of vitamin D receptor (VDR) and tuberculosis (TB) susceptibility has been investigated previously; however, the results were inconsistent and conflicting. In the present study, a meta-analysis was performed to assess the relationship between VDR FokI gene polymorphism and the risk of TB. MATERIAL AND METHODS: Databases including PubMed and Embase were searched for genetic association studies of FokI polymorphism of vitamin D receptor (VDR) and TB...
October 1, 2016: Archives of Medical Science: AMS
Qunying Hu, Zhengshuai Chen, Guinian Liang, Fangping Mo, Hengxun Zhang, Shilin Xu, Yuhe Wang, Longli Kang, Tianbo Jin
BACKGROUND: The vitamin D receptor (VDR) mediates the immunological function of vitamin D3, which activates macrophages, and vitamin D deficiency has been linked to tuberculosis risk. Single nucleotide polymorphisms (SNPs) in VDR may influence the function of vitamin D and susceptibility to tuberculosis. METHODS: This study included 217 patients with pulmonary tuberculosis (PTB) and 383 healthy subjects in a Tibetan Chinese population living in and near Xi'an. Association analyses of SNPs in VDR were performed with the SPSS 17...
September 5, 2016: BMC Infectious Diseases
Peter J Tebben, Ravinder J Singh, Rajiv Kumar
Hypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D...
October 2016: Endocrine Reviews
Imran Rizvi, Ravindra Kumar Garg, Amita Jain, Hardeep Singh Malhotra, Arvind Kumar Singh, Shantanu Prakash, Neeraj Kumar, Rajeev Garg, Rajesh Verma, Abbas Ali Mahdi, Praveen Kumar Sharma
INTRODUCTION: Vitamin D levels and genetic factors, vitamin D receptor (VDR) and Toll like receptor- 2 (TLR-2) gene single nucleotide polymorphisms (SNPs), determine susceptibility to pulmonary tuberculosis. We aimed to evaluate vitamin D deficiency, VDR and TLR-2 gene SNPs in tuberculous meningitis (TBM). METHODS: This case-control study included 130 subjects each in three arms (TBM, pulmonary tuberculosis and healthy control). This study was performed in a large tertiary care institution of North India...
October 2016: Infection
Kashaf Junaid, Abdul Rehman, David A Jolliffe, Tahir Saeed, Kristie Wood, Adrian R Martineau
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and the vitamin D binding protein (DBP) have been reported to modify the influence of vitamin D deficiency on susceptibility to active tuberculosis (TB) in the UK, but this phenomenon has not been investigated in settings with a high TB burden. SNPs in CYP2R1, which encodes a vitamin D 25-hydroxylase enzyme, are known to influence vitamin D status, but their potential role in determining susceptibility to TB has not previously been investigated in any setting...
May 10, 2016: BMC Pulmonary Medicine
Ajay Panwar, Ravindra Kumar Garg, Hardeep Singh Malhotra, Amita Jain, Arvind Kumar Singh, Shantanu Prakash, Neeraj Kumar, Rajiv Garg, Abbas Ali Mahdi, Rajesh Verma, Praveen Kumar Sharma
Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such asTLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated serum vitamin D, and VDR and TLR-2 gene polymorphisms in patients with spinal tuberculosis.This study comprised of 3 groups: spinal tuberculosis, pulmonary tuberculosis, and controls (each with 106 subjects). Enzyme-linked immunosorbent assay was used to measure vitamin D levels, and polymerase chain reaction-sequencing method was used to analyze VDR and TLR-2 gene polymorphisms...
April 2016: Medicine (Baltimore)
M Harishankar, P Selvaraj
Vitamin D receptor (VDR) gene variants have been shown to be regulating the immune response in tuberculosis. We studied the regulatory role of VDR promoter Cdx-2 and 3'UTR TaqI gene variants on chemokine levels from culture filtrate antigen (CFA) stimulated with or without 1,25(OH)2D3 treated peripheral blood mononuclear cells of 50 pulmonary tuberculosis patients (PTB) and 51 normal healthy controls (HCs). In CFA with 1,25(OH)2D3 treated cultures, the MIP-1α, MIP-1β, RANTES levels were significantly decreased in Cdx-2 AA genotype compared to GG genotype, while a significantly increased MIG level was observed in Cdx-2 AA genotype (p<0...
June 2016: Human Immunology
Nontobeko E Mvubu, Balakrishna Pillay, Junaid Gamieldien, William Bishai, Manormoney Pillay
Limited knowledge exists on pathways, networks and transcriptional factors regulated within epithelial cells by diverse Mycobacterium tuberculosis genotypes. This study aimed to elucidate these mechanisms induced in A549 epithelial cells by dominant clinical strains in KwaZulu-Natal, South Africa. RNA for sequencing was extracted from epithelial cells at 48 h post-infection with 5 strains at a multiplicity of infection of approximately 10:1. Bioinformatics analysis performed with the RNA-Seq Tuxedo pipeline identified differentially expressed genes...
March 2016: Tuberculosis
Amita Gupta, Grace Montepiedra, Akshay Gupte, Bret Zeldow, Jennifer Jubulis, Barbara Detrick, Avy Violari, Shabir Madhi, Raziya Bobat, Mark Cotton, Charles Mitchell, Stephen Spector
BACKGROUND: This study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children. METHODS: A case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.g. vitamin D receptor (VDR)], vitamin D levels [e...
2016: PloS One
Shih-Wei Lee, Tzu-Yi Chuang, Hsiu-Han Huang, Chi-Wei Liu, Yung-Hsi Kao, Lawrence Shih-Hsin Wu
BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to the activation of macrophages and the deficiency of vitamin D seems to be involved in the risk of tuberculosis (TB). The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D receptor binding protein (VDBP) may be influenced by polymorphisms in the VDR and VDBP genes. In this study, variation in the VDR and VDBP genes was investigated in a Taiwanese population with TB...
October 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Mohammad Jafari, Mohammad Reza Nasiri, Roozbeh Sanaei, Saber Anoosheh, Parisa Farnia, Adel Sepanjnia, Nader Tajik
The innate immune response drives early events in Mycobacterium tuberculosis infection. Since human genetic variation is an important determinant in the outcome of infection with M. tuberculosis, we typed polymorphisms in the innate immune molecules, such as natural-resistance-associated macrophage protein 1 (NRAMP1), Vitamin D receptor (VDR), Tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule1 (ICAM-1), Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in a case-control study of pulmonary tuberculosis in Iranian population...
April 2016: Infection, Genetics and Evolution
Allison E Reeme, Richard T Robinson
Tuberculosis (TB) is a significant human disease caused by inhalation of Mycobacterium tuberculosis. Left untreated, TB mortality is associated with a failure to resolve pulmonary immunopathology. There is currently widespread interest in using vitamin D3 (VitD3) as an adjunct therapy for TB because numerous in vitro studies have shown that VitD3 has direct and indirect mycobactericidal activities. However, to date, there have been no in vivo studies addressing whether VitD3 affects experimental TB outcome...
February 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Siswanto Siswanto, Lilik Zuhriyah, Kusworini Handono, Loeki Enggar Fitri, Sumarno Reto Prawiro
BACKGROUND: The innate immune response to tuberculosis infection may involve the increased production of nitric oxide and cathelicidin due to the up-regulated expression of the vitamin D receptor (VDR), though this proposed mechanism remains controversial. The aim of this study was to determine how the exposure of human monocytes to Mycobacterium tuberculosis (M. tuberculosis) DNA affects the production of nitric oxide and cathelicidin, as well as the expression of VDR. METHODS: This study was performed using monocytes obtained from healthy donors...
May 2015: Malaysian Journal of Medical Sciences: MJMS
Anuroopa Gupta, Harish Padh
Genetic polymorphism in Mannose Binding Lectin-2 (MBL-2) and Vitamin D Receptor (VDR) is known to influence the susceptibility to tuberculosis. The objective of the present study was to evaluate the frequency distribution of the MBL-2 promoter and structural polymorphism (-550 H/L, -221 Y/X, and +4 P/Q; R52C, G54D, and G57F) and VDR polymorphism (FokI, BsmI, TaqI, and ApaI) in healthy individuals of Indian population and comparative analysis with the global population. In Indian population, the frequency of VDR mutant alleles "f" for FokI, "b" for BsmI, "t" for TaqI, and "a" for ApaI was 25%, 54%, 30%, and 61%, respectively...
2015: Genetics Research International
Marek Fol, Magdalena Druszczynska, Marcin Wlodarczyk, Elzbieta Ograczyk, Wieslawa Rudnicka
Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (M.tb), remains a leading public health problem in most parts of the world. Despite the discovery of the bacilli over 100 years ago, there are still many unanswered questions about the host resistance to TB. Although one third of the world's population is infected with virulent M.tb, no more than 5-10% develop active disease within their lifetime. A lot of studies suggest that host genetic factors determine the outcome of M.tb-host interactions, however, specific genes and polymorphisms that govern the development of TB are not completely understood...
2015: Acta Biochimica Polonica
Mercedes Fernández-Mestre, Ángel Villasmil, Howard Takiff, Zhenia Fuentes Alcalá
Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis...
2015: Disease Markers
Jie Zeng, Longxiang Xie, Hongping Luo, Jianping Xie
Epigenetics of genes associated with tuberculosis susceptibility such as DNA methylation, posttranslational histone modifications, and non-coding RNA remain largely untapped field for better tuberculosis control. Many genes involved in tuberculosis susceptibility (e.g., NRAMP1 (SLC11A1), IFNG, NOS2A, VDR, ISG15, TACO, TLR1, TLR, IL18R1, chemokines, PADI, DUSP14, MBL, and MASP-2) have been subjected to epigenetic modification. Our summary of these modifications provides fresh insights into the pathogenesis of tuberculosis and inspires targets discovery for host-derived therapy...
2015: Critical Reviews in Eukaryotic Gene Expression
Antonio Neme, Veijo Nurminen, Sabine Seuter, Carsten Carlberg
Monocytes are important cells of the innate immune system that can differentiate into macrophages and dendritic cells. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), serves as a ligand of the nuclear receptor vitamin D receptor (VDR). A key physiological function of 1,25(OH)2D3 is the defense against pathogens, such as those causing tuberculosis, that involves the modulation of the monocyte transcriptome. THP-1 cells are an established model of human monocytes, for which the at present largest set of 1,25(OH)2D3-affected genome-wide data are available...
November 2016: Journal of Steroid Biochemistry and Molecular Biology
Surojit Sarkar, Martin Hewison, George P Studzinski, Yan Chun Li, Vandana Kalia
The discovery of vitamin D receptor (VDR) expression in immune cells has opened up a new area of research into immunoregulation by vitamin D, a niche that is distinct from its classical role in skeletal health. Today, about three decades since this discovery, numerous cellular and molecular targets of vitamin D in the immune system have been delineated. Moreover, strong clinical associations between vitamin D status and the incidence/severity of many immune-regulated disorders (e.g. infectious diseases, cancers and autoimmunity) have prompted the idea of using vitamin D supplementation to manipulate disease outcome...
2016: Critical Reviews in Clinical Laboratory Sciences
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