Methylation Status of VDR Gene and its Association with Vitamin D Status and VDR Gene Expression in Pediatric Tuberculosis Disease

Abstract

ABSTRACT Deficiency in circulatory vitamin D level and vitamin D receptor DNA methylation could be associated with weakened innate immune response and increased susceptibility to tuberculosis (TB) disease in children. Therefore, we aimed to study the effect of vitamin D receptor (VDR) gene methylation on plasma vitamin D level and the expression of the VDR gene in children with active-TB disease. A cross-sectional comparative study was conducted in 43 children with active-TB and 33 healthy control children (HC). The vitamin D level was measured in plasma, while the levels of VDR gene promoter methylation and VDR gene expression were measured in peripheral blood. Children with active-TB showed a significantly lower median vitamin D level than HC [Cases 17.18 ng/mL (IQR, 8.3–18.6 ng/mL); HC 41.34 ng/mL (IQR, 40.2–43.49 ng/mL) (p<0.0001)] and decreased mRNA expression level of VDR gene [Cases 0.51 (IQR, 0.40–0.70); HC 1.06 (IQR, 0.8–1.2) (p<0.0001)] and increased VDR DNA methylation [Cases 75% (IQR, 50–75%); HC 10% (IQR, 10–25%) (p<0.0001)]. The VDR hypermethylation is significantly associated with reduced vitamin D level and decreased expression level of VDR gene. Therefore this inverse association could be involved in the impairment in the VDR mediated cytolytic and antimicrobial effector cell response in pediatric TB disease.