The Marine Medical Research Institute of Guangdong Zhanjiang (GDZJMMRI), Southern Science and Engineering Guangdong Laboratory Zhanjiang, Guangdong Medical University, Zhanjiang, China; Department of Blood Transfusion, Peking University Shenzhen Hospital, Shenzhen, China.
Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, China.
Infect Genet Evol. 2020 Nov;85:104423. doi: 10.1016/j.meegid.2020.104423. Epub 2020 Jun 15.
Increasing evidence shows that the PI3K/AKT/mTOR pathway can be activated by a variety of stimulus in immune cells. Schistosomiasis Japonica is a serious threat to human health in some lakes of China.
We analyzed the potential associations between the hub gene (PTEN, mTOR, AKT1 and AKT2) polymorphisms of PI3K/AKT/mTOR pathway and S. japonica risk, including infection risk, as well as immunological hepatic fibrosis risk. An immune database named Database of Immune Cell Expression, Expression quantitative trait loci and Epigenomics (DICE) was used to analyze the expression profiles of the hub genes in 15 types of immune cells.
Of them, two SNPs rs2295080 (mTOR) and rs7254617 (AKT2) were found associated with the risk of infection and fibrosis. We also performed a multivariant Cox regression analysis and found that HBV infection may increase hepatic fibrosis in chronic schistosomiasis patients, instead of genetic polymorphisms on PI3K/AKT/mTOR pathway or any other factors. We also found the expressions of mTOR (RICTOR) and AKT2 in T cells were higher than those in monocyte cells. And, the expressions of PTEN, mTOR (RICTOR) and AKT1 reduced both in activated CD4 T cells and activated CD8 T cells.
We concluded that rs2295080 may be an important marker in the diagnosis of susceptibility to schistosomiasis infection. But HBV infection not rs2295080 could promote immunological liver damage with fibrosis in patients with chronic schistosomiasis infection.
越来越多的证据表明，PI3K/AKT/mTOR 通路可以被免疫细胞中的各种刺激激活。日本血吸虫病是中国一些湖泊地区人类健康的严重威胁。
我们分析了 PI3K/AKT/mTOR 通路的枢纽基因（PTEN、mTOR、AKT1 和 AKT2）多态性与日本血吸虫病风险之间的潜在关联，包括感染风险以及免疫性肝纤维化风险。我们使用了一个名为免疫细胞表达、表达数量性状基因座和表观基因组学数据库（DICE）的免疫数据库来分析 15 种免疫细胞中枢纽基因的表达谱。
其中，两个 SNP(rs2295080[mTOR]和 rs7254617[AKT2])与感染和纤维化风险相关。我们还进行了多变量 Cox 回归分析，发现 HBV 感染可能会增加慢性血吸虫病患者的肝纤维化，而不是 PI3K/AKT/mTOR 通路的遗传多态性或任何其他因素。我们还发现 mTOR（RICTOR）和 AKT2 在 T 细胞中的表达高于单核细胞中的表达。此外，PTEN、mTOR（RICTOR）和 AKT1 的表达在激活的 CD4 T 细胞和激活的 CD8 T 细胞中均降低。
我们得出结论，rs2295080 可能是诊断日本血吸虫病感染易感性的重要标志物。但是 HBV 感染而不是 rs2295080 可能会促进慢性血吸虫病感染患者的免疫性肝损伤和纤维化。
