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A Common OXTR Risk Variant Alters Regulation of Gene Expression by DNA Hydroxymethylation in Pregnant Human Myometrium.

Authors :
Danoff JS
Lillard TS
Myatt L
Connelly JJ
Erickson EN
Source :
Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2024 Oct; Vol. 31 (10), pp. 3132-3138. Date of Electronic Publication: 2024 Jun 11.
Publication Year :
2024

Abstract

Postpartum hemorrhage, or excessive bleeding after birth, is a leading cause of maternal morbidity. A major cause of postpartum hemorrhage is uterine atony, tiring of the uterus which leads to ineffective contractions. Uterine contractions depend on oxytocin signaling in the myometrium, which in turn depends on expression of the oxytocin receptor (OXTR). Both genetic and epigenetic factors related to the oxytocin receptor are associated with risk of postpartum hemorrhage, but a mechanism relating these factors to oxytocin receptor activity in myometrium remains unclear. We report a genetic by epigenetic interaction whereby the relationship between DNA hydroxymethylation and OXTR gene expression depends on a common OXTR gene variant (rs53576). We also provide evidence that a similar genetic by epigenetic interaction using blood-derived DNA methylation is associated with relevant clinical outcomes: quantity of oxytocin administration and odds for postpartum hemorrhage. These results provide new avenues for predicting how women will respond to pharmacological agents in the prevention and treatment of postpartum hemorrhage.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
1933-7205
Volume :
31
Issue :
10
Database :
MEDLINE
Journal :
Reproductive sciences (Thousand Oaks, Calif.)
Publication Type :
Academic Journal
Accession number :
38862858
Full Text :
https://doi.org/10.1007/s43032-024-01621-9