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

TITLE=Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine

JOURNAL=Frontiers in Genetics

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1187415

DOI=10.3389/fgene.2023.1187415

ISSN=1664-8021

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> We observed individual differences in the sedation and hemodynamics induced by DXM. <italic>ABCG2</italic> rs2231142, <italic>CYP2D6</italic> rs16947, <italic>WBP2NL</italic> rs5758550, <italic>KATP</italic> rs141294036, <italic>KCNMB1</italic> rs11739136, <italic>KCNMA1</italic> rs16934182, <italic>ABCC9</italic> rs11046209, <italic>ADRA2A</italic> rs1800544, and <italic>ADRB2</italic> rs1042713 were shown to cause statistically significant (<italic>p</italic> &lt; 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and <italic>ADRA2A</italic> rs1800544 are statistically related to the effective dose of DXM sedation.</p><p><bold>Discussion:</bold> 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.</p>