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

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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.

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Acknowledgements

This work was supported by National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (NRF-2017R1C1B5076675 and NRF-2017M3A9B6061511); and the Catholic Medical Center Research Foundation from the program year of 2017. Some of the Biospecimens and data used in this study were provided by the Biobank of Seoul National University Hospital, a member of Korea Biobank Network.

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Authors and Affiliations

  1. Department of Life Science, Dongguk University-Seoul, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea

    Minho Lee

  2. Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea

    Gunhee Lee

  3. Department of Pediatrics, Seoul National University, College of Medicine and Seoul National University Children’s Hospital, Seoul, Republic of Korea

    Hee Gyung Kang

  4. Department of Pediatrics, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon-Si, Gyeonggi-do, Republic of Korea

    Jin-Soon Suh

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  1. Minho Lee
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Correspondence to Jin-Soon Suh.

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Conflict of Interest

Minho Lee, Gunhee Lee, Hee Gyung Kang, and Jin-Soon Suh declare that they have no conflict of interest.

Ethical statement

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The trial was conducted in accordance with the Declaration of Helsinki and the Harmonized Tripartite Guideline for Good Clinical Practice from the International Conference on Harmonization. This study was reviewed and approved by the Institutional Review Boards of Bucheon St. Mary’s Hospital of the Catholic University of Korea (IRB No. HC18TNDI0012) and Seoul National University Hospital (No. 1808–157-967). All patients enrolled completed the informed consent form.

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Lee, M., Lee, G., Kang, H.G. et al. New susceptible locus, rs9428555, is associated with pediatric-onset immunoglobulin A nephropathy and immunoglobulin A vasculitis in Koreans. Genes Genom 43, 1049–1057 (2021). https://doi.org/10.1007/s13258-021-01120-0

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