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Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population
Premature ovarian failure (POF) is a complex disease of which the etiology is influenced by numerous genetic variations. Several POF candidate genes have been reported. However, no causal genes with high odds ratio (OR) have yet been discovered. This study included 564 females of Korean ethnicity, c...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720130/ https://www.ncbi.nlm.nih.gov/pubmed/33114509 http://dx.doi.org/10.3390/jpm10040193 |
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author | Park, JeongMan Park, YoungJoon Koh, Insong Kim, Nam Keun Baek, Kwang-Hyun Yun, Bo-Seong Lee, Kyung Ju Song, Jae Yun Lee, Eunil Kwack, KyuBum |
author_facet | Park, JeongMan Park, YoungJoon Koh, Insong Kim, Nam Keun Baek, Kwang-Hyun Yun, Bo-Seong Lee, Kyung Ju Song, Jae Yun Lee, Eunil Kwack, KyuBum |
author_sort | Park, JeongMan |
collection | PubMed |
description | Premature ovarian failure (POF) is a complex disease of which the etiology is influenced by numerous genetic variations. Several POF candidate genes have been reported. However, no causal genes with high odds ratio (OR) have yet been discovered. This study included 564 females of Korean ethnicity, comprising 60 patients with POF and 182 controls in the discovery set and 105 patients with POF and 217 controls in the replication set. We conducted genome-wide association analysis to search for novel candidate genes predicted to influence POF development using Axiom Precision Medicine Research Arrays and additive model logistic regression analysis. One statistically significant single nucleotide polymorphism (SNP), rs55941146, which encodes a missense alteration (Val > Gly) in the APBA3 gene, was identified with OR values for association with POF of 13.33 and 4.628 in the discovery and replication sets, respectively. No rs55941146 minor allele homozygotes were present in either cases or controls. The APBA3 protein binds FIH-1 that inhibits hypoxia inducible factor-1α (HIF-1α). HIF-1α contributes to granulosa cell proliferation, which is crucial for ovarian follicle growth, by regulating cell proliferation factors and follicle stimulating hormone-mediated autophagy. Our data demonstrate that APBA3 is a candidate novel causal gene for POF. |
format | Online Article Text |
id | pubmed-7720130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77201302020-12-08 Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population Park, JeongMan Park, YoungJoon Koh, Insong Kim, Nam Keun Baek, Kwang-Hyun Yun, Bo-Seong Lee, Kyung Ju Song, Jae Yun Lee, Eunil Kwack, KyuBum J Pers Med Article Premature ovarian failure (POF) is a complex disease of which the etiology is influenced by numerous genetic variations. Several POF candidate genes have been reported. However, no causal genes with high odds ratio (OR) have yet been discovered. This study included 564 females of Korean ethnicity, comprising 60 patients with POF and 182 controls in the discovery set and 105 patients with POF and 217 controls in the replication set. We conducted genome-wide association analysis to search for novel candidate genes predicted to influence POF development using Axiom Precision Medicine Research Arrays and additive model logistic regression analysis. One statistically significant single nucleotide polymorphism (SNP), rs55941146, which encodes a missense alteration (Val > Gly) in the APBA3 gene, was identified with OR values for association with POF of 13.33 and 4.628 in the discovery and replication sets, respectively. No rs55941146 minor allele homozygotes were present in either cases or controls. The APBA3 protein binds FIH-1 that inhibits hypoxia inducible factor-1α (HIF-1α). HIF-1α contributes to granulosa cell proliferation, which is crucial for ovarian follicle growth, by regulating cell proliferation factors and follicle stimulating hormone-mediated autophagy. Our data demonstrate that APBA3 is a candidate novel causal gene for POF. MDPI 2020-10-26 /pmc/articles/PMC7720130/ /pubmed/33114509 http://dx.doi.org/10.3390/jpm10040193 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Park, JeongMan Park, YoungJoon Koh, Insong Kim, Nam Keun Baek, Kwang-Hyun Yun, Bo-Seong Lee, Kyung Ju Song, Jae Yun Lee, Eunil Kwack, KyuBum Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population |
title | Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population |
title_full | Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population |
title_fullStr | Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population |
title_full_unstemmed | Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population |
title_short | Association of an APBA3 Missense Variant with Risk of Premature Ovarian Failure in the Korean Female Population |
title_sort | association of an apba3 missense variant with risk of premature ovarian failure in the korean female population |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720130/ https://www.ncbi.nlm.nih.gov/pubmed/33114509 http://dx.doi.org/10.3390/jpm10040193 |
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