Pharmacogenomics and Personalized Medicine (Feb 2022)
GABRA1 and GABRB2 Polymorphisms are Associated with Propofol Susceptibility
Abstract
Youjie Zeng,1 Si Cao,1 Minghua Chen,1 Chao Fang,1,2 Wen Ouyang1 1Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People’s Republic of ChinaCorrespondence: Wen Ouyang, Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China, Email [email protected]: To explore the effect of gene polymorphisms of propofol GABAA receptor and metabolic enzyme on drug susceptibility during the induction period of general anesthesia.Patients and Methods: A total of 294 female patients aged 18– 55 years, ASA I–II, who underwent hysteroscopy with intravenous general anesthesia, were included in the study. Anesthesia was induced by continuous intravenous infusion of propofol at 40 mg·kg− 1·h− 1. Infusion of propofol was ended when both the Modified Observer’s Assessment of Awareness/Sedation scale (MOAA/S scale) decreased to 1 and the BIS index decreased to 60. The time when the MOAA/S scale decreased to 1 and the time when BIS index decreased to 60 was recorded to assess the susceptibility to the sedation effect. The maximum decreased percentage in mean arterial pressure (MAP) within 5 minutes was recorded to assess the susceptibility of cardiovascular response. Venous blood of each patient was collected to identify the presence of genetic variants in the GABRA1, GABRA2, GABRB2, GABRB3, GABRG2, CYP2B6, and UGT1A9 genes using the Sequenom MassARRAY® platform.Results: After receiving propofol infusion, carriers of polymorphic GABRA1 rs4263535 G allele required significantly less time for BIS decreased to 60, while carriers of polymorphic GABRB2 rs3816596 T allele required significantly more time for BIS decreased to 60, carriers of polymorphic GABRA1 rs1157122 C allele and carriers of polymorphic GABRB2 rs76774144 T allele had a significantly less change in MAP.Conclusion: GABRB2 rs3816596 and GABRA1 rs4263535 polymorphisms are associated with susceptibility to the sedation effect of propofol. GABRA1 rs1157122 and GABRB2 rs76774144 polymorphisms are associated with the degree of drop in blood pressure after propofol infusion.Keywords: pharmacogenomics, drug susceptibility, GABAA receptor, CYP2B6, UGT1A9
