The Impact of CYP3A4, COMT V158M, and OPRM A118G Gene Polymorphisms on the Effectiveness of Sufentanil in Labor Analgesia

Summary

Here, we present a method to evaluate the impact of CYP3A4, COMT V158M, and OPRM1 A118G polymorphisms on sufentanil efficacy and maternal outcomes during labor analgesia, enabling pharmacogenetic analysis to guide personalized pain management.

Abstract

Genetic polymorphisms in CYP3A4, COMT V158M, and OPRM A118G may influence analgesic response, hemodynamic regulation, and postpartum recovery, while parity is thought to affect labor outcomes and adverse events. This study investigated how these genotypes and parity impact maternal and neonatal outcomes, labor duration, pain control, and postpartum complications in 380 pregnant women stratified by genotype. Data on baseline characteristics, labor duration, VAS pain scores, and postpartum adverse events were collected, and safety indicators such as blood pressure, heart rate, fetal outcomes, and Apgar scores were analyzed. Associations between parity and postpartum responses were explored using univariate and logistic regression models. Baseline variables were largely comparable across genotypes except for a higher BMI in the CYP3A4 CT/TT group. Sufentanil consumption was significantly higher in CYP3A4 CT/TT and OPRM A118G GA/GG carriers, although labor duration did not differ among genotypes. OPRM A118G GA/GG carriers also showed a higher incidence of fever (P = 0.016) and greater reductions in blood pressure after intervention (P < 0.001), though all groups achieved similar pain relief. Multiparas experienced less urinary retention (P = 0.005) but more pruritus (P = 0.011), and logistic regression confirmed smaller decreases in systolic blood pressure (OR = 1.049, P = 0.001) and lower risk of pruritus (OR = 0.326, P = 0.01) in this group. Although CYP3A4, COMT, and OPRM A118G genotypes did not broadly influence maternal or neonatal outcomes, carriers of CYP3A4 CT/TT and OPRM A118G GA/GG required higher sufentanil doses and displayed genotype-specific hemodynamic responses, while parity was associated with distinct adverse event profiles and blood pressure changes. These findings highlight the relevance of genetic polymorphisms and parity in guiding personalized postpartum care.

Introduction

Labor pain ranks among the most severe forms of pain a woman can experience. Effective pain management is crucial, not only for comfort but also to reduce associated stress and psychological distress^1,2. Inadequate control of labor pain may trigger shifts in maternal hormones, such as catecholamines and endorphins, which can lower pain thresholds and heighten anxiety about childbirth. This increased pain sensitivity may induce significant adverse emotional reactions in both the mother and fetus, potentially resulting in trauma^3,4. Therefore, pain relie....

Protocol

The reagents and equipment used in this study are listed in the Table of Materials.

1. Study design, setting, and participant selection

This prospective observational study investigated the effects of OPRM1 A118G, COMT V158M, and CYP3A4 genetic polymorphisms on the safety and efficacy of sufentanil for labor analgesia. Participants were recruited from women aged 18-45 years with uncomplicated singleton cephalic pregnancies between 37-42 weeks of gestation, who received labor analgesia at the study institution from September 1, 2020, to December 31, 2023. The study was conducted in ....

Results

General information
A schematic representation of the study framework is presented in Figure 1. A total of 380 eligible participants were identified. The mean (SD) age was 30.49 ± 3.87 years for the CYP3A4 CC group, 30.44 ± 3.68 years for the CYP3A4 CT/TT group, 30.53 ± 3.95 years for the COMT GG group, 30.40 ± 3.62 years for the COMT GA/AA group, 30.70 ± 3.89 years for the OPRM1 A118G AA group, and 30.30 ± 3.73 years for the OPRM1 A118G GA/GG group, with no significant .......

Discussion

This study aimed to investigate the effects of CYP3A4, COMT V158M, and OPRM genotypes on maternal and infant outcomes, duration of labor, postpartum adverse reactions, and visual analog scale (VAS) pain scores in 380 pregnant women. Key findings indicate that, although demographic factors were generally comparable across groups, women with the CYP3A4 CT/TT genotype had higher pre-pregnancy and prenatal BMI levels than those with the CYP3A4 CC genotype (P = 0.002 and P = 0.021, respectively). Moreover, s.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
16-Gauge Polyethylene Catheter	Smiths Medical	504-009	Used for tracheal intubation in rats
17-Gauge Tuohy Needle	B. Braun	331090	Used for epidural puncture at L3-L4
Annexin V-FITC	BD Biosciences	556547	Used in apoptosis detection with flow cytometry
Capillary Electrophoresis DNA Sequencer	Applied Biosystems	3730xl	Used to sequence PCR products for genotyping
Collagenase Type II	Worthington	LS004176	0.2%, for enzymatic digestion of cardiac tissue
DNA Extraction Kit	Qiagen	69504	Extracts genomic DNA from whole blood samples
Flow Cytometer (488 nm)	BD Biosciences	342940	Used to detect Annexin V-FITC/PI labeled cells
GeneMarker Software	SoftGenetics	GM2024	Used for SNP analysis and genotype calling
Generic Graphing Software	GraphPad	v9.5	Used for visualization of statistical data
Haploview Software	Broad Institute	v4.2	Used for Hardy-Weinberg equilibrium and LD analysis
Infusion Pump	Smiths Medical	CADD-5700	Used for continuous epidural drug infusion
Lidocaine	Not specified	Not specified	0.8%, 3 ml test dose for epidural test block
Nylon Suture (8-0)	Ethicon	W9823	Used for LAD coronary artery ligation in MIRI model
PCEA System	B. Braun	331090	Patient-controlled epidural analgesia system
PCR Purification Kit	Omega Bio-Tek	D2500-01	Purifies PCR products before sequencing
Pentobarbital Sodium	Merck	1.46005	3% solution, 50 mg/kg for anesthesia of rats
Polyethylene Tubing	Becton Dickinson	431432	Used to create reversible coronary ligation
Propidium Iodide (PI)	Sigma-Aldrich	P4170	Used at 5 µg/ml for apoptosis detection
Protease	Sigma-Aldrich	P5147	0.1%, used with collagenase for tissue digestion
Ropivacaine	Not specified	Not specified	0.08% concentration for labor analgesia
Statistical Software	IBM SPSS	v29.0	Used for RM-ANOVA, logistic regression, and PSM
Sufentanil	Not specified	Not specified	Used for epidural labor analgesia (0.3 µg/ml)
Taq DNA Ligase	New England Biolabs	M0208L	Used in LDR reaction for genotyping
Taq DNA Polymerase	Takara	RR001A	Used in PCR amplification for genotyping