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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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