The role of IFITM1 and IFITM3 in kidney disease

• Applicant: Dr. Bernhard Dumoulin
• Subject Area: Nephrology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 532136566

More than 10% of the global population is affected by chronic kidney disease (CKD), and its prevalence in Western countries is steadily increasing. There are a variety of diseases that can lead to chronic kidney disease, among those diabetes and arterial hypertension are the most prevalent. Gene expression analysis of kidney biopsies from patients with hypertensive and diabetic nephropathy has established sterile inflammation as a hallmark of CKD. While targeting immune pathways in CKD may prove beneficial, it can also lead to negative side effects. Hence, a better understanding of sterile inflammation in CKD is essential. Kidney function is highly heritable and therefore genome-wide association studies (GWAS), have significantly advanced out understanding about the genetic underpinnings of CKD. However, GWAS typically do not provide much insight into the underlying biological mechanisms or pathways involved, as more than 90% of the identified variants are in the non-coding region of the genome. To overcome this limitation, expression quantitative trait loci (eQTL) analysis can be used to prioritize causal genes by defining the genotype effect on gene expression. Combining GWAS and eQTL, we identified Interferon Induced Transmembrane Protein 1 (IFITM1) and IFITM3 as candidate genes for kidney disease. These genes belong to the IFITM family of proteins, which are activated by type I and type I interferons and act as antiviral factors that prevent the viral entry of pathogens like influenza A virus, HIV-1, and Dengue virus. We picked these candidates as we feel it could help to explain the excess inflammation in CKD. To understand the role of IFITM1 and IFITM3 in CKD, we plan to carry out a phenome-wide association study (PheWAS) and utilize state-of-the-art single-cell sequencing technologies in mouse models of chronic kidney disease.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professorin Dr. Katalin Susztak, Ph.D.