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

• Published in: Revista da Sociedade Brasileira de Medicina Tropical
• Main Authors: Juan He, Shengyuan Liu, Xujun Guo, Fan Zhang, Yuzheng Fan, Lijuan Wu, Howard Eugene Takiff, Yashuang Zhao
• Format: Article in Journal/Newspaper
• Language: English
• Published: Sociedade Brasileira de Medicina Tropical (SBMT) 2023
• Subjects: PI3K/AKT/mTOR; Autophagy; Tuberculosis; SNP; Genetic risk score; Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.1590/0037-8682-0104-2023; https://doaj.org/article/d8a6e95fffa84f2f9d1453a08605af91

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.