Impact of mTOR gene polymorphisms and gene-tea interaction on susceptibility to tuberculosis

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.

Impact of PD-1 gene polymorphism and its interaction with tea drinking on susceptibility to tuberculosis

“…Furthermore, according to the results of the marginal structural linear odds models, we discovered a negative interaction between rs7568402 of PD-1 genes and tea drinking, which indicated that tea drinking, consistent with our prior studies [ 5 , 28 ], was a protective factor in TB infection. Moreover, black tea, oolong and green tea were all confirmed to be inversely associated with TB and significant dose–response relationship was discovered [ 5 ].…”

“…The study participants included 503 TB patients and 494 controls. The distributions of demographic characteristics and associated risk factors between the TB patient group and the control group have been reported in our previous study [ 28 ]. The two groups exhibited no statistical difference ( P > 0.05) in terms of sex, age, marital status, educational background and alcohol drinking, while differences in BMI, history of BCG vaccination, smoking status and tea drinking were statistically significant ( P < 0.05).…”

“…Experimental studies also showed that increasing tea consumption could raise blood catechin levels, leading to increased plasma antioxidant activity and resistance to diseases [ 29 ]. Furthermore, tea polyphenols have been proposed to be responsible for the inverse relation due to their abilities of antioxidant and free radical scavenging anti-inflammation effect [ 4 , 28 ]. The polyphenol content of tea differs from different degree of fermentation and an inverse association is exhibited between the two variants.…”

Impact of MASP2 gene polymorphism and gene-tea drinking interaction on susceptibility to tuberculosis

“…We investigated the association of three MASP2 SNPs and TB susceptibility using a case–control study. There was a statistical difference in BMI, history of BCG vaccination, smoking and tea drinking between the case group and the control group (P < 0.05), but no statistical difference was found in gender, age, marital status, educational background and alcohol consumption (P > 0.05), the data was cited from reference 28 .…”

“…To exclude possible confounding risk factors, the occurrence of TB was used as the dependent variable, the rs12142107, rs12711521, and rs7548659 of MASP2 genes were used as the independent variables, and the sex, age, marital status, educational background, BMI, smoking status, alcohol drinking, and tea drinking were used as the covariates, and multivariate unconditional logistic regression analysis conducted. The additive interaction of marginal structural linear odds models were used for point estimation and interval estimation of the relative excess risk of interaction (RERI) to analyze the gene-environment interaction 28 . RERI > 0 suggests positive interactions.…”