Potential Similarities in Sex Difference in Key Genes and Their Expression, Network, EQTL and Pathways between COVID-19 and Chronic Kidney Disease Based on Mouse Model

Abstract

COVID-19 and chronic kidney disease (CKD) share similarity in sex bias and key genes in the disease pathway of sex difference. We investigated the sex difference of molecular pathways of four key players of these two diseases using an existing large set of whole genome expression profiles from the kidneys of female and male mouse models. Our data show that there is little to no correlation at the whole genome expression level between female and male mice among these four genes. There are considerable sex differences among genes in upstream regulation, Ace2 complex interaction, and downstream pathways. Snap25 and Plcb4 may play important roles in the regulation of the expression level of Adam17, Tmprss2, and Cd146 in females. In males, Adh4 is a candidate gene for the regulation of Adam17, while Asl, Auts2, and Rabger1 are candidates for Tmprss2. Within the Ace2 complex, Cd146 directly influences the expression level of Adam17 and Ace2 in the female, while in the male Adam potentially has a stronger influence on Ace2 than that of Tmprss2. Among the top 100 most related genes, only one or two genes from four key genes and 11 from the control B-Actin were found to be the same between sexes. Among the top 10 sets of genes in the downstream pathway of Ace2, only two sets are the same between the sexes. We concluded that these known key genes and novel genes in CKD may play significant roles in the sex difference in the CKD and COVID-19 disease pathways.