Exploration of susceptible genes associated with Henoch–Schönlein purpura by whole exome sequencing

Abstract

Background. Henoch-Schönlein purpura (HSP) is a systemic small-vessel vasculitis caused by environmental and inherent factors. Although recent research has advanced our understanding of the role of genetic susceptibility in HSP, there are still significant gaps in our knowledge. Objectives. In this study, we aimed to explore some susceptibility genes likely associated with HSP. Material and methods. Three DNA samples from a family with HSP were used to perform whole exome sequencing with Illumina Hiseq 2500 high-throughput sequencing. The relevant single nucleotide variants (SNVs) were screened according to specific filter conditions and the screened SNVs were then verified with Sanger sequencing. The Sanger sequencing results were further screened according to available literature. Finally, candidate genes were validated in 92 samples from children with HSP, and also in 1 child with HSP from HSP family, using the polymerase chain reaction technique (PCR). Results. Our analysis revealed that the MIF gene and the MGAT5 gene related to immunity remained after screening. Among the 93 children with HSP, there were 3 patients with MIF mutations and 2 patients with MGAT5 mutations. Conclusions. Our findings are helpful for providing new methods and ideas for understanding the pathogenesis of HSP by detecting and analyzing gene mutations at the whole-exome level including multi-generation sequencing. MIF and MGAT5 may be new susceptibility loci for HSP, but their roles in the pathogenesis of HSP are worthy of further study.

IgA vasculitis nephritis

“…Micro-RNAs that impact upon antibody glycosylation and receptor expression influence the course of the disease [15 ▪ ,38,43]. In addition, genes associated with the regulation of the innate immune system like MGAT5 (a negative regulator of T-cell activation thresholds) or Macrophage Migration Inhibitory Factor (MIF) seem to increase the susceptibility toward IgA vasculitis [44]. Differences in the occurrence of HLA polymorphisms associated with IgA vasculitis might explain ethnic differences in the incidence of the disease, which is highest in the Asian population [45].…”