Association Between UGT1A9 rs13418420 Polymorphism and Propofol Induction Characteristics in Chinese Female Patients...

Propofol, a commonly used intravenous sedative in general anesthesia, exhibits significant inter-individual variability in clinical effects; however, the underlying mechanisms remain uncertain. We aimed to assess the association between the UGT1A9 rs13418420 polymorphism and individual propofol response, as assessed by the time required for the bispectral index (BIS) to decrease to 60.

A total of 75 Chinese female patients undergoing painless abortion, cervical conization, or hysteroscopy under intravenous anesthesia without endotracheal intubation were recruited. Based on bioinformatic analysis and our preliminary sequencing experiments in the Chinese population, UGT1A9 rs13418420 was selected for genotyping and validated using quantitative PCR (qPCR). The primary outcome was the time required for BIS to decrease to 60. Secondary outcomes included the time required for BIS to recover to 80, plasma propofol concentrations measured at 1, 5, 10, and 15 minutes after administration, mean arterial pressure, and heart rate.

Our results revealed that patients with the TT genotype of UGT1A9 rs13418420 exhibited a shorter time for BIS to decrease to 60 (P <0.001, adjusted P <0.001) and higher plasma drug concentrations at 15 minutes compared to those with CC and CT genotypes (P=0.026, P=0.032). Linear mixed-effects model analysis of repeated plasma concentration measurements showed a significant time effect (P < 0.001), a trend toward an overall genotype effect (P = 0.063), and no significant genotype-by-time interaction (P = 0.885). No significant differences were observed in recovery-related outcomes among the three genotype groups.

Patients carrying the TT genotype of UGT1A9 rs13418420 exhibited a significantly shorter time to BIS 60 and higher plasma propofol concentrations at 15 minutes than those carrying the CC or CT genotypes. No significant differences were observed in recovery-related outcomes among the three genotype groups. These findings suggest that UGT1A9 rs13418420 polymorphism may contribute to inter-individual variability in the onset of propofol-induced anesthesia and warrant further investigation in larger studies.