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Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate
Tracy A Manuck1, Yinglei Lai, Paul J Meis
1Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network, Bethesda, MD, USA. tracy.manuck@hsc.utah.edu
American Journal of Obstetrics and Gynecology
|May 24, 2011
Summary
Single nucleotide polymorphisms in the progesterone receptor (PGR) gene may alter the effectiveness of 17-alpha-hydroxyprogesterone caproate (17-OHPC) in preventing recurrent preterm birth (PTB). Genetic variations influence treatment response in specific ethnic groups.
Area of Science:
- Reproductive genetics
- Pharmacogenomics
- Obstetrics
Background:
- Recurrent preterm birth (PTB) remains a significant challenge in maternal-fetal medicine.
- Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) is a treatment used to prevent recurrent PTB.
- The role of genetic factors in treatment response is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that single nucleotide polymorphisms (SNPs) in the progesterone receptor (PGR) gene influence the efficacy of 17-OHPC for preventing recurrent PTB.
- To identify specific PGR gene variants associated with differential responses to 17-OHPC treatment.
Main Methods:
- Secondary analysis of a randomized controlled trial comparing 17-OHPC and placebo for recurrent PTB prevention.
- Genotyping of 20 single nucleotide polymorphisms (SNPs) within the PGR gene.
- Multivariable logistic regression to assess treatment-genotype interactions on recurrent PTB risk.
Main Results:
- The study included 380 women, with 66.6% receiving 17-OHPC and 33.4% receiving placebo. 61.1% of participants were African American.
- Significant treatment-genotype interactions were observed for specific PGR SNPs (rs471767, rs578029, rs500760, rs503362, rs666553) in relation to PTB risk (<37 weeks and <32 weeks gestation).
- Interactions varied across different ethnic groups (African Americans, Hispanics/Caucasians).
Conclusions:
- Progesterone receptor (PGR) gene polymorphisms may significantly alter the clinical efficacy and safety of 17-OHPC in preventing recurrent preterm birth.
- These findings suggest a potential role for pharmacogenomic approaches in personalizing 17-OHPC treatment strategies.
- Further research is warranted to validate these genotype-specific treatment effects.
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