Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth: a case–control study

the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR)

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Objective: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB). Design: Case–control. Setting: Three tertiary-care centres across the USA. Population: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P. Methods: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P). Main outcome measures: To assess genetic variation, all women underwent whole exome sequencing. Between-group sequence variation was analysed with the Variant Annotation, Analysis, and Search Tool (VAAST). Genes scored by VAAST with P < 0.05 were then analysed with two online tools: (1) Protein ANalysis THrough Evolutionary Relationships (PANTHER) and (2) Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results: Using Definition A, there were 70 women with successful prolongation and 29 without; 1375 genes scored by VAAST had P < 0.05. Using Definition B, 47 women had successful prolongation and 52 did not; 1039 genes scored by VAAST had P < 0.05. PANTHER revealed key differences in gene ontology pathways. Many genes from definition A were classified as prematurity genes (P = 0.026), and those from definition B as pharmacogenetic genes (P = 0.0018); (P, non-significant after Bonferroni correction). Conclusion: A novel analytic approach revealed several genetic differences among women delivering early vs later with 17-P. Tweetable abstract: Several key genetic differences are present in women with recurrent preterm birth despite 17-P treatment.

Original languageEnglish (US)
Pages (from-to)343-350
Number of pages8
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Volume125
Issue number3
DOIs
StatePublished - Feb 1 2018

Keywords

  • 17-Alpha hydroxyprogesterone caproate
  • current preterm birth
  • pharmacogenomics
  • spontaneous prematurity

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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    the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR) (2018). Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth: a case–control study. BJOG: An International Journal of Obstetrics and Gynaecology, 125(3), 343-350. https://doi.org/10.1111/1471-0528.14485