Experimental Evaluation of ABCB1 C3435T (rs1045642) Gene Polymorphism and Its Association with Postoperative Analgesia in Hip Replacement Surgery

Summary

This study investigated whether a common genetic variant affects postoperative pain control following hip replacement. Patients with different genotypes showed clear differences in pain intensity, analgesic use, and pain-related biological responses.

Abstract

This study investigated the association between the ABCB1 (MDR1) C3435T (rs1045642) gene polymorphism and postoperative analgesia in patients undergoing hip replacement surgery. A total of 100 patients who underwent hip replacement in our hospital between January 2023 and January 2024 received postoperative patient-controlled intravenous analgesia with sufentanil. Preoperative serum samples were collected, and genomic detection was performed using the TaqMan SNP genotyping assay. According to the C3435T genotype, patients were classified into wild-type homozygotes (CC group), mutant heterozygotes (CT group), and mutant homozygotes (TT group). Clinical parameters, including baseline characteristics, Visual Analogue Scale (VAS) pain scores, sufentanil consumption, serum pain mediators (prostaglandin E2 (PGE2), substance P (SP), and β-endorphin (β-EP)), Hamilton anxiety and depression scores, sleep quality, and the incidence of adverse events within 24 h after surgery were compared among groups. Baseline characteristics were similar across groups (p > 0.05). VAS scores, sufentanil dosage, and serum PGE2, SP, and β-EP levels at 24 h were significantly lower in CT and TT groups compared with the CC group (p < 0.05). The TT group also exhibited reduced Hamilton anxiety and depression scores relative to both CC and CT groups (p < 0.05), whereas the CT group showed higher anxiety and depression scores than the CC group (p < 0.05). Sleep quality and adverse event rates were not significantly different among groups (p > 0.05). These findings suggest a potential association between the ABCB1 (MDR1) C3435T (rs1045642) polymorphism and variability in postoperative analgesic efficacy. Patients carrying the TT genotype tended to experience better analgesia, lower sufentanil requirements, and improved psychological outcomes. Although these results are promising, they should be interpreted with caution due to the small sample size and single-center design. Further large-scale studies are warranted to confirm these observations and evaluate their clinical applicability.

Introduction

Hip replacement refers to the replacement of the damaged hip joint with an artificial hip prosthesis through surgery. For early femoral head necrosis, hip osteoarthritis, and other diseases, the symptoms can be relieved, and the condition can be delayed through conservative treatment of integrated traditional Chinese and Western medicine¹. When the pain and deformity of the hip joint affect walking, it cannot be relieved by conservative treatment such as drugs, which seriously affects the quality of life. Hip replacement surgery can be chosen to relieve joint pain, rebuild hip function, and improve the quality of life. A series of pathophysiolo....

Protocol

This study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Fuzhou Hospital of Traditional Chinese Medicine (Approval No.: LC-2023-048). Written informed consent was obtained from all participants prior to enrollment.

Data and methods
Based on the research hypothesis, we developed a prospective cohort analysis study protocol. A total of 100 patients undergoing elective hip replacement surgery were prospectively enrolled, with a mean age of 58.41 ± 6.97 years. Figure 1 illustrates the technical roadmap of this protocol, w....

Results

Participant characteristics and genotype distribution
A total of 100 patients were enrolled and successfully genotyped for the ABCB1 C3435T polymorphism. The genotype distribution was 40.0% (40/100) for CC, 49.0% (49/100) for CT, and 11.0% (11/100) for TT. The allele frequencies were 64.5% for C (129/200) and 35.5% for T (71/200). The genotype distribution conformed to Hardy-Weinberg equilibrium (χ² =0.49, p=0.48; Table 1). Baseline characteristics, in.......

Discussion

Hip replacement is a common major orthopedic operation, and postoperative pain is one of the main problems faced by patients. The effect of postoperative analgesia is influenced by many factors, including individual factors such as the patient's age, gender, weight, and pain sensitivity, as well as external factors such as operation mode and postoperative rehabilitation exercise^13,14. In addition, the drug analgesia scheme is also an important factor affectin.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
0.9% Sodium Chloride Injection	Fresenius Kabi	19194	Diluent for sufentanil (PCIA solution) and other drugs; used for wound irrigation during surgery [document: "Postoperative PCIA", "Hip arthroplasty procedure"].
Allelic Discrimination Analysis Software (for real-time PCR)	Not specified (same as real-time PCR platform)	Not specified	Used for genotype calling of ABCB1 C3435T; requires call rate ≥95% and duplicate concordance 100% [document: "Genomic DNA extraction and SNP genotyping"].
Centrifuge (for serum/plasma separation)	Beckman Coulter	Avanti J - E	Operates at ~1000 × g (≈3000 rpm, 10 cm rotor radius); centrifuges blood samples for 10-20 min at room temperature to separate serum/plasma [document: "Blood sampling and processing"].
Cisatracurium Injection	Jiangsu Hengrui Pharmaceutical Co., Ltd	H20060869	Neuromuscular blocking agent for tracheal intubation, dose 0.1 mg/kg [document: "Anesthesia and intraoperative management"].
Clinical Chemistry Analyzer	Roche Diagnostics	Cobas c 501	Detects serum biomarkers (PGE2, SP, β-EP) [document: "Pain mediator assays"].
EDTA Anticoagulant	BD Vacutainer	366450	Used for preoperative venous blood collection (5 mL) for genomic DNA extraction and genotyping; samples mixed by gentle inversion to prevent coagulation [document: "Study design and participants", "Blood sampling and processing"].
Electrocardiograph (ECG)	Philips	CardioPerfect MX800	Part of standard intraoperative monitoring [document: "Anesthesia and intraoperative management"].
EndNote	Clarivate Analytics	X9	Assists in reference management and formatting (aligns with journal citation norms) [reference: "JoVE_Materials.xls"].
End-Tidal Carbon Dioxide (ETCO2) Monitor	Masimo	Rad - 97	Part of standard intraoperative monitoring; used to maintain normocapnia [document: "Anesthesia and intraoperative management"].
Low-Temperature Refrigerator (-80°C/-20°C)	Haier	DW - 86L626 (-80°C); DW - 25L262 (-20°C)	-80°C for storing aliquoted serum/plasma; -20°C for storing extracted genomic DNA [document: "Blood sampling and processing", "Genomic DNA extraction and SNP genotyping"].
Midazolam Injection	Jiangsu Enhua Pharmaceutical Co., Ltd	H10980025	Anesthesia induction agent, dose 0.05 mg/kg [document: "Anesthesia and intraoperative management"].
Non-Invasive Blood Pressure Monitor	Omron	HEM - 9072T	Part of standard intraoperative monitoring [document: "Anesthesia and intraoperative management"].
Programmable Intravenous Analgesia (PCIA) Pump	Phoenix Pharmaceuticals	EK-022-16	Used for postoperative sufentanil delivery; settings: background infusion 1 mL/h, bolus dose 1 mL, lockout interval 10 min; records cumulative sufentanil consumption [document: "Postoperative PCIA"].
Propofol Injection	AstraZeneca	H20120088	Anesthesia induction (titrated to loss of consciousness) and maintenance (0.08-0.12 mg·kg-1·min-1) [document: "Anesthesia and intraoperative management"].
Prostaglandin E2 (PGE2) Radioimmunoassay Kit	Cayman Chemical	514010	Validated kit for serum PGE2 detection; run in duplicate, with intra-assay CV ≤10% and inter-assay CV ≤15% (repeated if exceeding limits) [document: "Pain mediator assays"].
Pulse Oximeter			Part of standard intraoperative monitoring (measures SpO2) [document: "Anesthesia and intraoperative management"].
Real-Time PCR Platform	Phoenix Pharmaceuticals	EK-022-16	Used for ABCB1 C3435T genotyping; thermal cycling conditions: enzyme activation, 40 cycles of denaturation (95°C, ~15 s) and annealing/extension (60°C, ~60 s) [document: "Genomic DNA extraction and SNP genotyping"].
Silica-Membrane Column-Based Genomic DNA Extraction Kit	Qiagen	51104	Used for extracting genomic DNA from whole blood; procedures include cell lysis, protein digestion, DNA adsorption, sequential washes, and elution in 100 μL elution buffer [document: "Genomic DNA extraction and SNP genotyping"].
Spectrophotometer	Thermo Fisher Scientific	NanoDrop One	Measures DNA concentration and purity; samples with A260/280 ≈1.8-2.0 considered acceptable [document: "Genomic DNA extraction and SNP genotyping"].
SPSS	IBM Corporation	26	Used for statistical analysis: Shapiro-Wilk normality test, Levene’s test, ANOVA, Kruskal-Wallis test, χ² test, etc. [document: "Statistical analysis"; reference: "JoVE_Materials.xls"].
Substance P (SP) Radioimmunoassay Kit	Merck Millipore	RAB0456	Validated kit for serum SP detection; same quality control standards as PGE2 kit [document: "Pain mediator assays"].
Sufentanil Injection	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	NA	Used for anesthesia induction (0.4 μg/kg), intraoperative maintenance (0.15-0.30 μg·kg-1·h-1), and postoperative PCIA (1.5 μg/mL diluted in 0.9% saline) [document: "Anesthesia and intraoperative management", "Postoperative PCIA"].
TaqMan SNP Genotyping Assay (for ABCB1 C3435T, rs1045642)	Qiagen	51104	Pre-designed allele-specific hydrolysis-probe assay for real-time PCR genotyping of ABCB1 C3435T polymorphism [document: "Genomic DNA extraction and SNP genotyping"].
Tracheal Intubation Equipment (laryngoscope, endotracheal tube)	Draeger	Capnomac Ultima	Used for tracheal intubation after confirmation of neuromuscular blockade [document: "Anesthesia and intraoperative management"].
Volume-Controlled Ventilator	Dräger	Primus	Used for intraoperative mechanical ventilation; settings: respiratory rate ~15 breaths/min, tidal volume 6-8 mL/kg predicted body weight [document: "Anesthesia and intraoperative management"].
β-Endorphin (β-EP) Sandwich Immunoassay Kit	Phoenix Pharmaceuticals	EK-022-16	Validated kit for serum β-EP detection; calibration curves generated with ≥5 standards [document: "Pain mediator assays"].