Potential correlation assessment identified by a genome-wide association study using induced pluripotent stem cells from patients with IgAN

Abstract

It is unclear whether genetic mutations associated with inflammation and mitochondrial function are involved in the progression and exacerbation of immunoglobulin A nephropathy (IgAN). In this study, we aimed to investigate the IgAN genetic background.

Genome-wide association studies (GWAS) were performed using four lines of human-induced pluripotent stem cells (hiPSCs) established from two patients with IgAN, possible IgAN, and minimal change disease.

There were 4641 single nucleotide polymorphisms (SNPs) in hiPSCs derived from patients with IgAN or possible IgAN compared to those in hiPSCs derived from minimal change disease as a control. We identified genes expressed more frequently than those in hiPSCs derived from minimal change disease. We identified SNP-inhibited genes that were significantly associated with inflammation (115 SNPs), oxidative stress (29 SNPs), fibrosis (10 SNPs), and mitochondrial function (158 SNPs).

Our GWAS, using hiPSCs derived from patients with IgAN or possible IgAN, indicated that these mutations may be linked to mitochondrial dysfunction, inflammation, and extracellular matrix production.