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Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study

IgA nephropathy (IgAN) is an autoimmune disorder which is believed to be non-monogenic. We performed an exome-wide association study of 70 children with IgAN and 637 healthy donors. The HLA allele frequencies were compared between the patients and healthy donors from the bone marrow registry of the...

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Autores principales: Buianova, Anastasiia A., Proskura, Mariia V., Cheranev, Valery V., Belova, Vera A., Shmitko, Anna O., Pavlova, Anna S., Vasiliadis, Iuliia A., Suchalko, Oleg N., Rebrikov, Denis V., Petrosyan, Edita K., Korostin, Dmitriy O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647220/
https://www.ncbi.nlm.nih.gov/pubmed/37958966
http://dx.doi.org/10.3390/ijms242115984
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author Buianova, Anastasiia A.
Proskura, Mariia V.
Cheranev, Valery V.
Belova, Vera A.
Shmitko, Anna O.
Pavlova, Anna S.
Vasiliadis, Iuliia A.
Suchalko, Oleg N.
Rebrikov, Denis V.
Petrosyan, Edita K.
Korostin, Dmitriy O.
author_facet Buianova, Anastasiia A.
Proskura, Mariia V.
Cheranev, Valery V.
Belova, Vera A.
Shmitko, Anna O.
Pavlova, Anna S.
Vasiliadis, Iuliia A.
Suchalko, Oleg N.
Rebrikov, Denis V.
Petrosyan, Edita K.
Korostin, Dmitriy O.
author_sort Buianova, Anastasiia A.
collection PubMed
description IgA nephropathy (IgAN) is an autoimmune disorder which is believed to be non-monogenic. We performed an exome-wide association study of 70 children with IgAN and 637 healthy donors. The HLA allele frequencies were compared between the patients and healthy donors from the bone marrow registry of the Pirogov University. We tested 78,020 gene markers for association and performed functional enrichment analysis and transcription factor binding preference detection. We identified 333 genetic variants, employing three inheritance models. The most significant association with the disorder was observed for rs143409664 (PRAG1) in the case of the additive and dominant models (P(BONF) = 1.808 × 10(−15) and P(BONF) = 1.654 × 10(−15), respectively), and for rs13028230 (UBR3) in the case of the recessive model (P(BONF) = 1.545 × 10(−9)). Enrichment analysis indicated the strongly overrepresented “immune system” and “kidney development” terms. The HLA-DQA1*01:01:01G allele (p = 0.0076; OR, 2.021 [95% CI, 1.322–3.048]) was significantly the most frequent among IgAN patients. Here, we characterized, for the first time, the genetic background of Russian IgAN patients, identifying the risk alleles typical of the population. The most important signals were detected in previously undescribed loci.
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spelling pubmed-106472202023-11-05 Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study Buianova, Anastasiia A. Proskura, Mariia V. Cheranev, Valery V. Belova, Vera A. Shmitko, Anna O. Pavlova, Anna S. Vasiliadis, Iuliia A. Suchalko, Oleg N. Rebrikov, Denis V. Petrosyan, Edita K. Korostin, Dmitriy O. Int J Mol Sci Article IgA nephropathy (IgAN) is an autoimmune disorder which is believed to be non-monogenic. We performed an exome-wide association study of 70 children with IgAN and 637 healthy donors. The HLA allele frequencies were compared between the patients and healthy donors from the bone marrow registry of the Pirogov University. We tested 78,020 gene markers for association and performed functional enrichment analysis and transcription factor binding preference detection. We identified 333 genetic variants, employing three inheritance models. The most significant association with the disorder was observed for rs143409664 (PRAG1) in the case of the additive and dominant models (P(BONF) = 1.808 × 10(−15) and P(BONF) = 1.654 × 10(−15), respectively), and for rs13028230 (UBR3) in the case of the recessive model (P(BONF) = 1.545 × 10(−9)). Enrichment analysis indicated the strongly overrepresented “immune system” and “kidney development” terms. The HLA-DQA1*01:01:01G allele (p = 0.0076; OR, 2.021 [95% CI, 1.322–3.048]) was significantly the most frequent among IgAN patients. Here, we characterized, for the first time, the genetic background of Russian IgAN patients, identifying the risk alleles typical of the population. The most important signals were detected in previously undescribed loci. MDPI 2023-11-05 /pmc/articles/PMC10647220/ /pubmed/37958966 http://dx.doi.org/10.3390/ijms242115984 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Buianova, Anastasiia A.
Proskura, Mariia V.
Cheranev, Valery V.
Belova, Vera A.
Shmitko, Anna O.
Pavlova, Anna S.
Vasiliadis, Iuliia A.
Suchalko, Oleg N.
Rebrikov, Denis V.
Petrosyan, Edita K.
Korostin, Dmitriy O.
Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study
title Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study
title_full Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study
title_fullStr Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study
title_full_unstemmed Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study
title_short Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study
title_sort candidate genes for iga nephropathy in pediatric patients: exome-wide association study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647220/
https://www.ncbi.nlm.nih.gov/pubmed/37958966
http://dx.doi.org/10.3390/ijms242115984
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