# The effects of oxytocin receptor genetic variants on oxytocin response

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2020 · $31,438

## Abstract

PROJECT SUMMARY/ABSTRACT
Oxytocin is used to induce or augment labor in about half of patients (2 million per year) who deliver in US
hospitals. The oxytocin dose required to induce labor varies about 20-fold between individuals, with some
patients requiring high doses of oxytocin that have been linked to both maternal and fetal complications. To avoid
these adverse effects, obstetricians need to be able to predict each individual's oxytocin dose requirement and
tailor their approach to labor management accordingly. Previous studies suggest that genetic variations in the
oxytocin receptor (OXTR) gene contribute to the vast variation in oxytocin dose requirement, but the mechanisms
by which these variants act are unknown. The proposed research elucidates the effects of both rare missense
single nucleotide variants (mSNVs) and common noncoding single nucleotide polymorphisms (SNPs) on OXTR
function and expression and on uterine response to oxytocin. Aim 1 of this proposal investigates the hypothesis
that OXTR mSNVs identified in individuals who responded to high or low doses of oxytocin modulate OXTR's
ligand binding and signaling capabilities. This aim will examine the effect of mSNVs on OXTR's ability to bind
oxytocin, to recruit its signaling partners β-arrestin and Gq, and to potentiate key pro-labor signaling pathways.
Aim 2 investigates the hypothesis that noncoding SNPs in OXTR alter OXTR expression and thereby modulate
uterine sensitivity to oxytocin. Analysis of allele-specific OXTR expression will be used to identify functional SNPs
that may modulate OXTR expression. Finally, this Aim will determine the effects of OXTR SNPs and variations
in OXTR expression on oxytocin response in myometrial cells from patient samples. In the long term, the
proposed work will aid the development of individualized approaches for labor management that will minimize
the risk of oxytocin overdose and the ensuing potentially fatal outcomes.
The candidate has assembled a multidisciplinary mentorship team, led by sponsor Dr. Sarah England, that will
ground her training in the study of uterine physiology, genetics, and clinical and translational science. The
candidate's institution, Washington University School of Medicine, has a long history of supporting MD-PhD
students and physician-scientists at all stages of their training. By conducting this research, the candidate will
acquire valuable research experience that will help her become an independent physician-scientist working to
translate findings from genetic studies to functional impacts on physiology and human health.

## Key facts

- **NIH application ID:** 10016110
- **Project number:** 5F30HD097925-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Manasi Malik
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,438
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016110

## Citation

> US National Institutes of Health, RePORTER application 10016110, The effects of oxytocin receptor genetic variants on oxytocin response (5F30HD097925-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016110. Licensed CC0.

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