Vitamin D and the promoter methylation of its metabolic pathway genes in association with the risk and prognosis of tuberculosis.

ABSTRACT:

Background

A variety of abnormalities in vitamin D metabolism have been reported in patients with active tuberculosis. However, intervention trials have produced inconsistent results. We hypothesized that genetic and epigenetic changes in the key genes of the vitamin D metabolic pathway may partly explain the differences between studies.

Methods

We performed a case-control study followed by a prospective cohort study. We recruited 122 patients with pulmonary tuberculosis and 118 healthy controls. The serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were measured. The methylation of the promoter regions of key genes in the vitamin D metabolic pathway (CYP24A1, CYP27A1, CYP27B1, CYP2R1, and VDR) was detected using the Illumina MiSeq platform. The specific methylation profiles were examined as epigenetic biomarkers. The sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to estimate the predictive value of the biomarkers.

Results

The baseline serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations in the cases were significantly lower than those in the controls (51.60?±?27.25 nmol/L vs. 117.50?±?75.50 nmol/L, Z?=?-?8.515, P?interaction?=?4.11, 95% CI 1.26-13.36, P?=?0.019). The serum 1,25-dihydroxyvitamin D concentration at the end of the intensive treatment stage was related to a patient's prognosis (P?=?0.008). There were 23 CpG sites that were individually related to the treatment outcomes, but the relationships were not significant after the Bonferroni correction.

Conclusion

Both serum vitamin D concentrations and the methylation levels of key genes in the vitamin D metabolic pathway are related to the risk and prognosis of tuberculosis.

SUBMITTER: Wang M 

PROVIDER: S-EPMC6136159 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature