Association of PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population.

BACKGROUND: Autophagy can inhibit the survival of intracellular microorganisms including Mycobacterium tuberculosis (Mtb), and the PI3K/AKT/mTOR pathway plays a crucial role. This study investigated the association between PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms and pulmonary tuberculosis (PTB) susceptibility. METHODS: KEGG pathway and gene ontology (GO) databases were searched for genes belonging to the PI3K/AKT/mTOR and autophagy pathways. Thirty SNPs in nine genes were identified and tested for their associations with tuberculosis in 130 patients with PTB and 271 controls. We constructed genetic risk scores (GRSs) and divided the participants into 3 subgroups based on their GRSs:0-5, 6-10, and 11-16. RESULTS: This analysis revealed that the AKT1 (rs12432802), RPTOR (rs11654508, rs12602885, rs2090204, rs2589144, and rs2672897), and TSC2 (rs2074969) polymorphisms were significantly associated with PTB risk. A decreasing trend was observed (P trend 0.020), in which a lower GRS was associated with a higher risk of PTB ([6-10] vs. [0-5]: OR (95%CI) 0.590 (0.374-0.931); [11-16] vs. [0-5]: OR (95%CI) 0.381 (0.160-0.906)). CONCLUSIONS: Polymorphisms in AKT1, RPTOR, and TSC2 may influence susceptibility to PTB.

Association of PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population

ABSTRACT Background: Autophagy can inhibit the survival of intracellular microorganisms including Mycobacterium tuberculosis (Mtb), and the PI3K/AKT/mTOR pathway plays a crucial role. This study investigated the association between PI3K/AKT/mTOR pathway autophagy-related gene polymorphisms and pulmonary tuberculosis (PTB) susceptibility. Methods: KEGG pathway and gene ontology (GO) databases were searched for genes belonging to the PI3K/AKT/mTOR and autophagy pathways. Thirty SNPs in nine genes were identified and tested for their associations with tuberculosis in 130 patients with PTB and 271 controls. We constructed genetic risk scores (GRSs) and divided the participants into 3 subgroups based on their GRSs:0-5, 6-10, and 11-16. Results: This analysis revealed that the AKT1 (rs12432802), RPTOR (rs11654508, rs12602885, rs2090204, rs2589144, and rs2672897), and TSC2 (rs2074969) polymorphisms were significantly associated with PTB risk. A decreasing trend was observed (P trend 0.020), in which a lower GRS was associated with a higher risk of PTB ([6-10] vs. [0-5]: OR (95%CI) 0.590 (0.374-0.931); [11-16] vs. [0-5]: OR (95%CI) 0.381 (0.160-0.906)). Conclusions: Polymorphisms in AKT1, RPTOR, and TSC2 may influence susceptibility to PTB.

An Investigation of the Risk Factors Associated With Anti-Tuberculosis Drug-Induced Liver Injury or Abnormal Liver Functioning in 757 Patients With Pulmonary Tuberculosis.

Objectives: To identify the risk factors associated with anti-tuberculosis drug-induced liver injury (AT-DILI) or abnormal living functioning from 757 patients with pulmonary tuberculosis (TB) registered at Nanshan Center for Chronic Disease Control (Nanshan CCDC), Shenzhen, Guangdong Province, China. Design and methods: We identified 757 TB patients who met our inclusion criteria by screening the Hospital Information System (HIS) at Nanshan CCDC. Next, we identified positive cases of AT-DILI or abnormal liver functioning based on results of the first-time liver function tests (LFTs) after taking anti-TB drugs. The χ2 test was used to relate the positive rate with a variety of factors. A logistic regression model was also used to identify statistically significant risk factors. Results: Of the 757 patients, the positive rate of AT-DILI or abnormal liver functioning was 37.9% (287/757). Univariate analysis revealed that the positive rate was 42.91% (212/494) for males and 28.52% (75/263) for females. The positive rate was significantly higher in males (p <0.001). Patients with an annual income of 9,231-13,845 USD had a significantly higher positive rate (67.35%; 33/49) than those with an income of 1,540-4616 USD (37.97%; 30/79) (p = 0.022). The most frequent prescription regime among positive cases was a 2 months supply of fixed dose combination Ethambutol Hydrochloride, Pyrazinamide, Rifampicin and Isoniazid Tablets (Ⅱ) 450 mg) followed by a 4 months supply of fixed dose combination Rifampin and Isoniazid Capsules (2FDC-HRZE half/4FDC-HR) at 56.03% (144/257). The least frequent prescription regime was a 2 months supply of fixed dose combination Rifampin, Isoniazid and Pyrazinamide Capsules with Ethambutol independently followed by a 4 months supply of fixed dose combination Rifampin and Isoniazid Capsules (2FDC-HRZ + EMB/4FDC-HR) at 24.27% (25/103). The difference between these two different regimes was significant (p = 0.022). With an increase in the duration of medication, patients under various prescription regimes all showed a gradual increase in the positive rate of AT-DILI or abnormal liver functioning. Conclusion: We identified several risk factors for the occurrence of AT-DILI or abnormal liver functioning, including gender, annual income, prescription regime, dosage, and treatment time.

A Comprehensive App That Improves Tuberculosis Treatment Management Through Video-Observed Therapy: Usability Study.

BACKGROUND: Treatment of pulmonary tuberculosis (TB) requires at least six months and is compromised by poor adherence. In the directly observed therapy (DOT) scheme recommended by the World Health Organization, the patient is directly observed taking their medications at a health post. An alternative to DOT is video-observed therapy (VOT), in which the patients take videos of themselves taking the medication and the video is uploaded into the app and reviewed by a health care worker. We developed a comprehensive TB management system by using VOT that is installed as an app on the smartphones of both patients and health care workers. It was implemented into the routine TB control program of the Nanshan District of Shenzhen, China. OBJECTIVE: The aim of this study was to compare the effectiveness of VOT with that of DOT in managing the treatment of patients with pulmonary TB and to evaluate the acceptance of VOT for TB management by patients and health care workers. METHODS: Patients beginning treatment between September 2017 and August 2018 were enrolled into the VOT group and their data were compared with the retrospective data of patients who began TB treatment and were managed with routine DOT between January 2016 and August 2017. Sociodemographic characteristics, clinical features, treatment adherence, positive findings of sputum smears, reporting of side effects, time and costs of transportation, and satisfaction were compared between the 2 treatment groups. The attitudes of the health care workers toward the VOT-based system were also analyzed. RESULTS: This study included 158 patients in the retrospective DOT group and 235 patients in the VOT group. The VOT group showed a significantly higher fraction of doses observed (P<.001), less missed observed doses (P<.001), and fewer treatment discontinuations (P<.05) than the DOT group. Over 79.1% (186/235) of the VOT patients had >85% of their doses observed, while only 16.4% (26/158) of the DOT patients had >85% of their doses observed. All patients were cured without recurrences. The VOT management required significantly (P<.001) less median patient time (300 minutes vs 1240 minutes, respectively) and transportation costs (¥53 [US $7.57] vs ¥276 [US $39.43], respectively; P<.001) than DOT. Significantly more patients (191/235, 81.3%) in the VOT group preferred their treatment method compared to those on DOT (37/131, 28.2%) (P<.001), and 92% (61/66) of the health care workers thought that the VOT method was more convenient than DOT for managing patients with TB. CONCLUSIONS: Implementation of the VOT-based system into the routine program of TB management was simple and it significantly increased patient adherence to their drug regimens. Our study shows that a comprehensive VOT-based TB management represents a viable and improved evolution of DOT.