Published online Oct 6, 2020. doi: 10.12998/wjcc.v8.i19.4320
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
Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis. The incidence of TB has been shown to vary among different races, ethnic groups, and families, indicating that host genetics influence TB susceptibility. mTOR gene is a key component of the PI3K/Akt/mTOR signaling pathway, and its dysregulation is associated with various diseases. In addition, several studies have demonstrated that tea is a protective factor against TB due to its antioxidant and free radical scavenging effects.
Investigations have suggested that polymorphisms of the mTOR gene are associated with susceptibility to various diseases. And epigallocatechin-3-gallate, the major component of tea catechins, could effectively activate PI3K/Akt signaling, leading to the activation of mTOR and inhibition of autophagy. The role of mTOR polymorphisms in TB is still inconclusive. Moreover, whether there is any interaction on TB risk between tea drinking and polymorphisms of mTOR gene has not been reported.
This study aimed to investigate 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.
In this case-control study, 503 TB patients 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.
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 of mTOR genes and tea drinking was 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.
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. These findings are significant for identifying populations with high risk of developing TB, and suggest that preventive measures through promoting the consumption of tea should be emphasized in the high-risk populations.
Since TB is a complex disease involving various factors including heredity, biology and environment, the genetic background of the study population or the difference in environmental exposure may lead to an inevitable heterogeneity between studies. Hence, larger independent population-based studies in different countries or ethnic groups are required to validate our initial findings.