The associations of hub gene polymorphisms in PI3K/AKT/mTOR pathway and Schistosomiasis Japonica infection and hepatic fibrosis

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.