Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 6, 2020; 8(19): 4320-4330
Published online Oct 6, 2020. doi: 10.12998/wjcc.v8.i19.4320
Impact of mTOR gene polymorphisms and gene-tea interaction on susceptibility to tuberculosis
Mian Wang, Shu-Juan Ma, Xin-Yin Wu, Xian Zhang, Julius Abesig, Zheng-Hui Xiao, Xin Huang, Hai-Peng Yan, Jing Wang, Meng-Shi Chen, Hong-Zhuan Tan
Mian Wang, Meng-Shi Chen, Hong-Zhuan Tan, Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
Shu-Juan Ma, Xin-Yin Wu, Julius Abesig, Jing Wang, Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
Xian Zhang, Department of Occupational and Environmental Hygiene, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan Province, China
Zheng-Hui Xiao, Hai-Peng Yan, Hunan Provincial Key Laboratory of Pediatric Emergency, Hunan Children’s Hospital, Changsha 410007, Hunan Province, China
Xin Huang, Department of Epidemiology and Health Statistics, Hunan Normal University, Changsha 410008, Hunan Province, China
Author contributions: Wang M and Ma SJ contributed to data analysis and writing of the manuscript; Wu XY, Zhang X and Huang X contributed to the data collection, data analysis and discussion; Xiao ZH, Yan HP and Wang J contributed to the literature search, language editing, and manuscript revision; Abesig J and Tan HZ contributed to the language editing and manuscript revision; Chen MS contributed to the study design, manuscript revision and study supervision; all authors approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81803298; and Hunan Provincial Natural Science Foundation, No. 2020JJ4762.
Institutional review board statement: The study was reviewed and approved by the Medical Ethical Committee of Xiangya School of Public Health Central South University, No. XYGW-2018-11.
Informed consent statement: All study participants gave informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Meng-Shi Chen, PhD, Lecturer, Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, No. 110 Xiangya Road, Changsha 410078, Hunan Province, China. 121444639@qq.com
Received: June 4, 2020
Peer-review started: June 4, 2020
First decision: July 25, 2020
Revised: July 30, 2020
Accepted: August 29, 2020
Article in press: August 29, 2020
Published online: October 6, 2020
Processing time: 115 Days and 23.9 Hours
Abstract
BACKGROUND

mTOR gene is a key component of the PI3K/Akt/mTOR signaling pathway, and its dysregulation is associated with various diseases. Several studies have demonstrated that tea drinking is a protective factor against tuberculosis (TB). This study was designed to explore five single nucleotide polymorphisms (SNPs) of mTOR in the Han population of China to determine how their interactions with tea drinking affect susceptibility to TB.

AIM

To investigate if the polymorphisms of mTOR gene and the gene-tea interaction are associated with susceptibility to TB.

METHODS

In this case-control study, 503 patients with TB and 494 healthy controls were enrolled by a stratified sampling method. The cases were newly registered TB patients from the county-level centers for disease control and prevention, and the healthy controls were permanent residents from Xin’ansi Community, Changsha city. Demographic data and environmental exposure information including tea drinking were obtained from the study participants. We genotyped five potentially functional SNP sites (rs2295080, rs2024627, rs1057079, rs12137958, and rs7525957) of mTOR gene and assessed their associations with the risk of TB using logistic regression analysis, and marginal structural linear odds models were used to estimate the gene-environment interactions.

RESULTS

The frequencies of four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) were found to be associated with susceptibility to TB (P < 0.05). Genotypes GT (OR 1.334), GG (OR 2.224), and GT + GG (OR 1.403) at rs2295080; genotypes CT (OR 1.562) and CT + TT (OR 1.578) at rs2024627, genotypes CT (OR 1.597), CC (OR 2.858), and CT + CC (OR 1.682) at rs1057079; and genotypes CT (OR 1.559) and CT + CC (OR 1.568) at rs7525957 of mTOR gene were significantly more prevalent in TB patients than in healthy controls. The relative excess risk of interaction between the four SNPs (rs2295080, rs2024627, rs1057079, and rs7525957) of mTOR genes and tea drinking were found to be -1.5187 (95%CI: -1.9826, -1.0547, P < 0.05), -1.8270 (95%CI: -2.3587, -1.2952, P < 0.05), -2.3246 (95%CI: -2.9417, -1.7076, P < 0.05) and -0.4235 (95%CI: -0.7756, -0.0714, P < 0.05), respectively, which suggest negative interactions.

CONCLUSION

The polymorphisms of mTOR (rs2295080, rs2024627, rs1057079, and rs7525957) are associated with susceptibility to TB, and there is a negative interaction between each of the four SNPs and tea drinking.

Keywords: Tuberculosis; mTOR; Tea drinking; Gene-environment interaction; The relative excess risk of interaction; Single nucleotide polymorphism

Core Tip: Our data demonstrated that genotypes GT, GG, and GT + GG at rs2295080; genotypes CT and CT + TT at rs2024627; genotypes CT, CC and CT + CC at rs1057079; and genotypes CT and CT + CC at rs7525957 of mTOR gene are associated with increased risk of tuberculosis in a Chinese population. In addition, there was a negative interaction between each of the four single nucleotide polymorphism (SNPs) and tea drinking. These findings may be helpful for identifying high-risk populations of tuberculosis, and suggest that promoting tea drinking might be a new way to reduce the risk of tuberculosis for individuals with mutations in the four SNPs.