Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine

Yuanyuan Ding; Aiqing Liu; Yafeng Wang; Shuai Zhao; Shiqian Huang; Hongyu Zhu; Lulin Ma; Linlin Han; Shaofang Shu; Lidong Zheng; Xiangdong Chen

doi:10.3389/fgene.2023.1187415

Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine

Front Genet. 2023 Aug 24:14:1187415. doi: 10.3389/fgene.2023.1187415. eCollection 2023.

Authors

Affiliations

¹ Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Anesthesiology, Lu'an Hospital Affiliated to Anhui Medical University, Lu'an, China.

^# Contributed equally.

Abstract

Introduction: Dexmedetomidine (DXM) is widely used as an adjuvant to anesthesia or a sedative medicine, and differences in individual sensitivity to the drug exist. This study aimed to investigate the effect of genetic polymorphisms on these differences. Methods: A total of 112 patients undergoing hand surgery were recruited. DXM 0.5 μg/kg was administered within 10 min and then continuously injected (0.4 μg/kg/h). Narcotrend index, effective dose and onset time of sedation, MAP, and HR were measured. Forty-five single nucleotide polymorphisms (SNPs) were selected for genotype. Results: We observed individual differences in the sedation and hemodynamics induced by DXM. ABCG2 rs2231142, CYP2D6 rs16947, WBP2NL rs5758550, KATP rs141294036, KCNMB1 rs11739136, KCNMA1 rs16934182, ABCC9 rs11046209, ADRA2A rs1800544, and ADRB2 rs1042713 were shown to cause statistically significant (p < 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and ADRA2A rs1800544 are statistically related to the effective dose of DXM sedation. Discussion: The evidence suggests that the nine SNPs involved in transport proteins, metabolic enzymes, and target proteins of DXM could explain the individual variability in the sedative and hemodynamic effects of DXM. Therefore, with SNP genotyping, these results could guide personalized medication and promote clinical and surgical management.

Keywords: dexmedetomidine; pharmacogenomics; sedation; single nucleotide polymorphism; susceptibility.

Grants and funding

This work was supported by the National Key Research and Development Program of China (grant number 2018YFC2001802, XC); Hubei Province Key Research and Development Program (grant number 2021BCA145, XC); and National Natural Science Foundation (grant number 82071251, XC).