New susceptible locus, rs9428555, is associated with pediatric-onset immunoglobulin A nephropathy and immunoglobulin A vasculitis in Koreans

Genes Genomics. 2021 Sep;43(9):1049-1057. doi: 10.1007/s13258-021-01120-0. Epub 2021 Jun 19.

Abstract

Background: Immunoglobulin A nephropathy (IgAN) is one of the most common primary forms of glomerulonephritis, while IgA vasculitis (IgAV) is the most common systemic vasculitis in children.

Objective: Herein we aimed to uncover single nucleotide polymorphism (SNP) markers associated with these two related diseases by applying association tests and Sanger sequencing.

Methods: Within the discovery stage, genomic DNA in blood samples from 101 enrolled patients were genotyped by the Korean Biobank Array. Association tests were performed with 397 Korean reference genomes. In the validation stage, 26 independent samples were genotyped by Sanger sequencing.

Results: Four SNPs were identified (P < 5 × 10-8) in the discovery stage. To determine whether the genotypes determined by SNP array were accurate, additional genotyping via Sanger sequencing was performed. As a result, only one SNP, rs9428555, was properly genotyped. In the validation stage, the minor allele (A > G) was found in as many as 15 out of 26 samples (minor allele frequency = 0.288), even though this minor allele is rare in East Asians (< 3%).

Conclusions: We found rs9428555 as a novel susceptible locus associated with the development of both IgAN and IgAV in Koreans. Though we cannot conclude rs9428555 is the unique susceptible locus of IgAN and IgAV, it is likely a good marker as the minor allele of this SNP occurred much more often in the patient group here versus within East Asians as a whole.

Keywords: Calcitriol; Child; Glomerulonephritis; IGA; Polymorphism; Purpura; Receptors; Schoenlein–Henoch; Single nucleotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / pathology
  • Child
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Glomerulonephritis, IGA / epidemiology
  • Glomerulonephritis, IGA / genetics*
  • Humans
  • IgA Vasculitis / epidemiology
  • IgA Vasculitis / genetics*
  • Immunoglobulin A / genetics*
  • Male
  • Obsessive-Compulsive Disorder / genetics*
  • Obsessive-Compulsive Disorder / pathology
  • Polymorphism, Single Nucleotide / genetics
  • Republic of Korea / epidemiology

Substances

  • Immunoglobulin A

Supplementary concepts

  • Pediatric acute-onset neuropsychiatric syndrome