title: Vitamin D status, vitamin D receptor and toll like receptor-2 polymorphisms in tuberculous meningitis: a case-control study.
abstract: BACKGROUND
  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. Subjects were enrolled from August 2013 to July 2015. Vitamin D levels were measured using enzyme immunoassay. SNPs in VDR and TLR-2 gene were assessed using polymerase chain reaction-sequencing method. TBM patients were followed for 6 months.
  
  
  RESULTS
  Vitamin D deficiency was significantly more common in TBM compared to controls and pulmonary tuberculosis (TBM versus controls p < 0.001; TBM versus pulmonary tuberculosis p < 0.001). The heterozygous (TC) and mutant (CC) genotypes of Taq1 VDR SNP were significantly associated with TBM as compared to controls [TC; p < 0.001, odds ratio (OR) = 3.53 (1.95-6.40); CC; p = 0.002 OR = 5.97 (1.89-18.84)]. The heterozygous genotypes were significantly associated with TBM as compared with pulmonary tuberculosis [p = 0.001; OR = 2.53(1.43-4.45)]. Heterozygous (TG) and mutants (GG) forms of Apa1 VDR SNPs were significantly associated with TBM compared to controls [TG; p = 0.001, OR = 2.86 (1.58-5.17), GG; p = 0.002, OR = 5.11 (1.80-14.54)] and pulmonary tuberculosis. There was no significant difference in the frequency of TLR-2 SNPs. No association was found between outcome of TBM and vitamin D deficiency, VDR or TLR-2 SNPs.
  
  
  CONCLUSIONS
  Vitamin D deficiency and VDR polymorphisms are associated with the susceptibility of TBM.
authors.affiliation: Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, 226003, India.
authors.forename: Imran
authors.initials: I
authors.lastname: Rizvi
authors.affiliation: Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, 226003, India. garg50@yahoo.com.
authors.forename: Ravindra Kumar
authors.initials: RK
authors.lastname: Garg
authors.affiliation: Department of Microbiology, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Amita
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, 226003, India.
authors.forename: Hardeep Singh
authors.initials: HS
authors.lastname: Malhotra
authors.affiliation: Department of Microbiology, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Microbiology, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Prakash
authors.affiliation: Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, 226003, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Pulmonary Medicine, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Garg
authors.affiliation: Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, 226003, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Verma
authors.affiliation: Department of Biochemistry, King George Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Mahdi
authors.affiliation: Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, 226003, India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000378:metabolism; D014390:Tuberculosis, Meningeal / Q000235:genetics* / Q000382:microbiology; D014807:Vitamin D / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C579457:VDR protein, human; D014807:Vitamin D
keywords: Single nucleotide polymorphisms; Toll like receptor 2; Vitamin D; Vitamin D receptor