CYP3A4*1G genetic polymorphism influences CYP3A activity and response to fentanyl in Chinese gynecologic patients.
OBJECTIVE
To investigate whether the CYP3A4*1G genetic polymorphism contributes to the variability in CYP3A activity and response to fentanyl.


METHODS
One hundred and forty-three gynecologic patients who were scheduled to undergo abdominal total hysterectomy or myomectomy with general anesthesia were enrolled in this study. Intravenous fentanyl patient-controlled analgesia was provided postoperatively for satisfactory analgesia. The degrees of pain at rest during PCA treatment were assessed with visual analog scale. The fentanyl consumption and occurrence of any adverse effects were recorded in the first 24 h postoperatively. CYP3A activity was measured by plasma 1'-hydroxymidazolam-to-midazolam ratio 1 h after intravenous administration of 0.1 mg/kg midazolam. CYP3A4*1G variant allele was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.


RESULTS
The frequency of the CYP3A4*1G variant allele was 0.269 in 143 Chinese gynecologic patients. The activity of CYP3A4 in patients homozygous for the *1G/*1G variant (0.34 +/- 0.15) was significantly lower than that in patients bearing the wild-type allele (*1/*1) (0.46 +/- 0.14) or in patients heterozygous for the *1/*1G variant (0.46 +/- 0.12) (P < 0.05). The patients with the CYP3A4*1G/*1G genotype needed less fentanyl (227.8 +/- 55.2 microg) to achieve pain control than patients carrying the CYP3A4*1/*1 (381.6 +/- 163.6 microg) and CYP3A4*1/*1G (371.9 +/- 180.1 microg) genotypes (P < 0.05) during the first 24 h postoperatively. There was no significant difference in incidence of adverse events among the different genotype groups (P > 0.05).


CONCLUSIONS
CYP3A4*1G genetic polymorphism decreases CYP3A activity and fentanyl consumption for postoperative pain control.
Department of Anesthesiology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Wei
W
Zhang
Yan-Zi
YZ
Chang
Quan-Cheng
QC
Kan
Li-Rong
LR
Zhang
Zhi-Song
ZS
Li
Hui
H
Lu
Zhong-Yu
ZY
Wang
Qin-Jun
QJ
Chu
Jie
J
Zhang
D000483:Alleles; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000627:therapeutic use*; D005787:Gene Frequency; D005838:Genotype; D013509:Gynecologic Surgical Procedures; D006801:Humans; D007262:Infusions, Intravenous; D008874:Midazolam / Q000031:analogs & derivatives / Q000097:blood; D010149:Postoperative Pain / Q000188:drug therapy* / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
D000701:Analgesics, Opioid; C040081:1-hydroxymethylmidazolam; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008874:Midazolam; D005283:Fentanyl