Assessment of global DNA methylation in children with tuberculosis disease

Studying DNA methylation changes in disease condition provides the basis of disease pathogenesis or host immune response to infection. Evidences suggest that pathogen-mediated DNA methylation changes influences the expression pattern of genes contributing to disease condition to avert host immune response. Hence, we attempted to study the association between tubercle bacilli-mediated global DNA methylation changes in children with tuberculosis (TB) disease and healthy controls.

Forty-three children diagnosed with TB and 33 healthy children were enrolled in this study. ELISA-based global DNA methylation quantification was performed to measure the changes in percentage of global genomic DNA methylation level.

Highly significant difference in global DNA methylation level was found between cases and controls and median global DNA methylation level was 6.25% (interquartile range [IQR] 2.5%-10%) in cases and 25% (IQR, 12.5%-25%) in controls (P < 0.001). Significant difference was found in GeneXpert-positive cases (P < 0.01). Receiver operating curve analysis showed that area under curve 0.81 for the total study population and 0.76 for GeneXpert-positive cases.

The results show the significant difference in global DNA methylation level in children with TB disease that can serve as a potential biomarker in early diagnosis of TB disease. Measuring global DNA methylation level, however, not an accurate or sensitive diagnostic method but evaluating active demethylation at genome-wide level can be used to monitor disease progression and treatment efficacy.