Effect of CYP2B6 Polymorphism on Differences in Effective Propofol Concentration

Objectives: Significant individual differences in sensitivity to anesthetic agent propofol is observed in clinical practice. The basis of high intersubject variability of propofol metabolism has not been sufficiently known yet. The present study aimed to investigate the effects of genetic polymorphisms on metabolic and functional pathways. Therefore, we investigated the association of genetic polymorphisms (rs3745274) with the effect of propofol.
Methods: This was a retrospective cohort study using anesthesia records of patients. Enrolled in this study were 144 patients (60 males and 84 females) who were scheduled to undergo cosmetic orthognathic surgery (upper and lower jawbone osteotomy) for bimaxillary protrusion at Tokyo Dental College hospital. We investigated the latency to loss of consciousness, the effect-site concentration (EC) of propofol, the bispectral index (BIS) and total dosage propofol after general anesthesia was induced into a loss of consciousness. In addition, we gathered blood samples under general anesthesia. After total genomic DNA was extracted from whole-blood samples using standard procedures, the rs3745274 polymorphism in the CYP2B6 gene was genotyped using TaqMan method (Thermo Fisher Scientific Inc., Waltham, MA, USA) with a LightCycler 480 (Roche Diagnostics, Mannheim, Germany).
Results: The EC of propofol until losing consciousness was significantly low among woman subjects carrying the CYP2B6 rs3745274 T/T genotype compared with subjects without the T/T genotype (p=0.0235). This result suggests that subjects carrying T/T genotype exhibited higher response to propofol than subjects without the T/T genotype.
Conclusions: The present reports provide individual differences in the propofol effect. Our results demonstrated the relationships between the CYP2B6 gene polymorphism (rs3745274) genotypes and individual sensitivities to propofol. Thus, the rs3745274 was identified as one of the possible determinant factors among pharmacokinetic and/or pharmacodynamic factors of propofol in patients under general anesthesia. Additionally, the rs3725274 may serve to a marker to avoid side effects including intraoperative awareness and delayed emergence from anesthesia.