GABRA1 and GABRB2 Polymorphisms are Associated with Propofol Susceptibility

Youjie Zeng; Si Cao; Minghua Chen; Chao Fang; Wen Ouyang

doi:10.2147/PGPM.S348170

GABRA1 and GABRB2 Polymorphisms are Associated with Propofol Susceptibility

Pharmgenomics Pers Med. 2022 Feb 9:15:105-117. doi: 10.2147/PGPM.S348170. eCollection 2022.

Authors

Youjie Zeng¹, Si Cao¹, Minghua Chen¹, Chao Fang^{1

2}, Wen Ouyang¹

Affiliations

¹ Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People's Republic of China.
² Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, People's Republic of China.

Abstract

Purpose: To explore the effect of gene polymorphisms of propofol GABA_A 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: CYP2B6; GABAA receptor; UGT1A9; drug susceptibility; pharmacogenomics.