Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate

Am J Obstet Gynecol. 2011 Aug;205(2):135.e1-9. doi: 10.1016/j.ajog.2011.03.048. Epub 2011 Apr 8.

Abstract

Objective: Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms in the human progesterone receptor (PGR) affect response to 17-OHPC in the prevention of recurrent PTB.

Study design: We conducted secondary analysis of a study of 17-OHPC vs placebo for recurrent PTB prevention. Twenty PGR gene single nucleotide polymorphisms were studied. Multivariable logistic regression assessed for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB.

Results: A total of 380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. In all, 61.1% of women were African American. Multivariable logistic regression demonstrated significant treatment-genotype interactions (either a beneficial or harmful treatment response) for African Americans delivering<37 weeks' gestation for rs471767 and rs578029, and for Hispanics/Caucasians delivering<37 weeks' gestation for rs500760 and <32 weeks' gestation for rs578029, rs503362, and rs666553.

Conclusion: The clinical efficacy and safety of 17-OHPC for recurrent PTB prevention may be altered by PGR gene polymorphisms.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • 17 alpha-Hydroxyprogesterone Caproate
  • Double-Blind Method
  • Female
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Humans
  • Hydroxyprogesterones / administration & dosage*
  • Infant, Newborn
  • Infant, Premature
  • Logistic Models
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / drug effects
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Pregnancy Outcome*
  • Premature Birth / drug therapy*
  • Premature Birth / genetics*
  • Premature Birth / prevention & control
  • Prospective Studies
  • Receptors, Progesterone / drug effects
  • Receptors, Progesterone / genetics*
  • Reference Values
  • Risk Assessment
  • Secondary Prevention
  • Treatment Outcome

Substances

  • Hydroxyprogesterones
  • Receptors, Progesterone
  • 17 alpha-Hydroxyprogesterone Caproate

Grants and funding