Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth: a case-control study.
BJOG
; 125(3): 343-350, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-28139890
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 OUTCOMEMEASURES:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nascimento Prematuro
/
Caproato de 17 alfa-Hidroxiprogesterona
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Pregnancy
País/Região como assunto:
America do norte
Idioma:
En
Revista:
BJOG
Assunto da revista:
GINECOLOGIA
/
OBSTETRICIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos