Vitamin D status, vitamin D receptor and toll like receptor-2 polymorphisms in tuberculous meningitis: a case-control study.

Abstract

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). 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 6months. 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. Vitamin D deficiency and VDR polymorphisms are associated with the susceptibility of TBM.