Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine
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 ha...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-08-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1187415/full |
| _version_ | 1797737599586009088 |
|---|---|
| author | Yuanyuan Ding Aiqing Liu Yafeng Wang Shuai Zhao Shiqian Huang Hongyu Zhu Lulin Ma Linlin Han Shaofang Shu Lidong Zheng Xiangdong Chen |
| author_facet | Yuanyuan Ding Aiqing Liu Yafeng Wang Shuai Zhao Shiqian Huang Hongyu Zhu Lulin Ma Linlin Han Shaofang Shu Lidong Zheng Xiangdong Chen |
| author_sort | Yuanyuan Ding |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T13:30:45Z |
| format | Article |
| id | doaj.art-b10ce86ad8fb4acc9637ac0c450eaa50 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T13:30:45Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-b10ce86ad8fb4acc9637ac0c450eaa502023-08-24T13:32:02ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-08-011410.3389/fgene.2023.11874151187415Genetic polymorphisms are associated with individual susceptibility to dexmedetomidineYuanyuan Ding0Aiqing Liu1Yafeng Wang2Shuai Zhao3Shiqian Huang4Hongyu Zhu5Lulin Ma6Linlin Han7Shaofang Shu8Lidong Zheng9Xiangdong Chen10Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Lu’an Hospital Affiliated to Anhui Medical University, Lu’an, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fgene.2023.1187415/fulldexmedetomidinepharmacogenomicssedationsingle nucleotide polymorphismsusceptibility |
| spellingShingle | Yuanyuan Ding Aiqing Liu Yafeng Wang Shuai Zhao Shiqian Huang Hongyu Zhu Lulin Ma Linlin Han Shaofang Shu Lidong Zheng Xiangdong Chen Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine Frontiers in Genetics dexmedetomidine pharmacogenomics sedation single nucleotide polymorphism susceptibility |
| title | Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine |
| title_full | Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine |
| title_fullStr | Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine |
| title_full_unstemmed | Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine |
| title_short | Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine |
| title_sort | genetic polymorphisms are associated with individual susceptibility to dexmedetomidine |
| topic | dexmedetomidine pharmacogenomics sedation single nucleotide polymorphism susceptibility |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1187415/full |
| work_keys_str_mv | AT yuanyuanding geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT aiqingliu geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT yafengwang geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT shuaizhao geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT shiqianhuang geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT hongyuzhu geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT lulinma geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT linlinhan geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT shaofangshu geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT lidongzheng geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine AT xiangdongchen geneticpolymorphismsareassociatedwithindividualsusceptibilitytodexmedetomidine |