Related Experiment Video
Updated: Mar 8, 2026
09:04
Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
Published on: September 10, 2018
10.2K
Pharmacogenomics of 17-alpha hydroxyprogesterone caproate for recurrent preterm birth: a case-control study
T A Manuck1,2,3, W S Watkins4, M S Esplin1,2
1Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
BJOG : an International Journal of Obstetrics and Gynaecology
|February 1, 2017
Summary
Maternal genotypes differ between women with recurrent preterm birth who deliver early versus late, even with 17-alpha hydroxyprogesterone caproate (17-P) treatment. Genetic variations impact pregnancy prolongation success.
Area of Science:
- Genetics
- Reproductive Medicine
- Perinatology
Background:
- Recurrent preterm birth (PTB) poses significant risks.
- 17-alpha hydroxyprogesterone caproate (17-P) is used for PTB prevention.
- Maternal genetic factors may influence treatment efficacy.
Purpose of the Study:
- To compare maternal genotypes between women with and without successful pregnancy prolongation during 17-P treatment for recurrent PTB.
- To identify genetic variations associated with differential response to 17-P therapy.
Main Methods:
- Case-control study involving 99 women with prior spontaneous PTB receiving 17-P.
- Whole exome sequencing and variant analysis using VAAST.
- Gene ontology pathway analysis using PANTHER and DAVID.
Main Results:
- Two definitions of successful prolongation identified distinct gene sets.
- Definition A (≥3 weeks later) associated with 1375 genes, Definition B (term delivery) with 1039 genes.
- Pathway analysis indicated differences in prematurity and pharmacogenetic genes between groups.
Conclusions:
- Novel analytic approach revealed genetic differences in women with varying responses to 17-P.
- Key genetic variations are present in women experiencing recurrent PTB despite 17-P treatment.
- These findings may inform personalized PTB prevention strategies.
Related Concept Videos
01:29Pharmacogenomics: Identification of New Drug Targets
56
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
56
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
76
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
76
01:27Pharmacogenetics of Drug Metabolism: Overview
77
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
77
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
60
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
60
01:28Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
79
Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
79
01:29Pharmacogenetics and Pharmacogenomics: Overview
98
Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
98