TB is the leading cause of mortality worldwide. Moreover, type 2 diabetes mellitus (T2DM) patients are three times more likely to develop TB. These individuals suffer worse disease progression, higher relapse rates, and greater mortality. A study published in the journal Frontiers in Endocrinology revealed the key gene involved in this progression.

Research material was collected from publicly available databases of TB and diabetes patients, using a combination of differential gene analysis, weighted gene co-expression network analysis (WGCNA), and machine learning models. 

The analysis of these databases using various machine learning models narrowed the targets down to three genes- CYP1B1, SERPING1, and CHPT1. Further, the functional analysis and validative and predictive modelling for these genes were performed using different techniques. Following these, the THP-1 macrophage was used under high glucose conditions to observe the gene activity.
 

Out of the three gene candidates, the CYP1B1 was found to be the best candidate. It was highly upregulated in high sugar environments when exposed to TB antigens. Activation of this gene further upregulated the production of inflammatory cytokines (including TNF-α, IL-6, IL-1β), and it disturbed the balance between innate and adaptive immunity. It also activated the NOD2–TRAF6–NF-κB signalling pathway, which is known to trigger hyperinflammation. Knocking down the CYP1B1 gene with siRNA reduced this progression. 

These findings explain the reason for the severity of TB in T2DM patients. High sugar concentration activates the CYP1B1 gene, which pushes the immune system into an inflammatory overdrive, solidifying its role as a crosstalk gene between the two major diseases. Using this data, the CYP1B1 gene is an excellent candidate as a diagnostic marker and a therapeutic target.