Association of an apba3 missense variant with risk of premature ovarian failure in the korean female population

Jeongman Park, Youngjoon Park, Insong Koh, Nam Keun Kim, Kwang Hyun Baek, Bo Seong Yun, Kyung Ju Lee, Jae Yun Song, Eunil Lee, Kyubum Kwack

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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-1a (HIF-1a). HIF-1a 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.

Original languageEnglish
Article number193
Pages (from-to)1-11
Number of pages11
JournalJournal of Personalized Medicine
Issue number4
Publication statusPublished - 2020 Dec


  • Autophagy
  • Cell proliferation
  • Follicle stimulating hormone
  • Genome-wide association study
  • Hypoxia-inducible factor 1
  • Ovarian follicle
  • Primary ovarian failure

ASJC Scopus subject areas

  • Medicine (miscellaneous)


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