中国汉族人群中肾上腺素α_(2A)受体基因多态性与右美托咪定心血管效应的相关性研究（英文）
|
摘要
目的:通过对右美托咪定静脉输注的临床研究,评价中国汉族人群中肾上腺素α_(2A)受体基因多态性与右美托咪定心血管效应的相关性。创新点:探索右美托咪定的心血管系统反应与肾上腺素α_(2A)受体基因多态性的关系,期望为临床个体化应用右美托咪定及其他α2受体激动剂提供重要的依据。方法:本研究取得单位伦理委员会的批准,所有受试者告知受试内容并签署知情同意书。60例美国麻醉医师协会Ⅰ–Ⅱ行择期手术汉族患者根据标准入选本研究。通过静脉输注右美托咪定,记录收缩压、舒张压、心率等心血管效应数据,并用聚合酶链式反应(PCR)法检测ADRA2A基因单核苷酸多态性。结论:中国汉族人群中肾上腺素α_(2A)受体C-1291G基因多态性与应用右美托咪定后心率变化有相关性。
There are differences in individual cardiovascular responses to the administration of dexmedetomidine, a highly selective α_(2A)-adrenergic receptor(ADRA2A) agonist. The aim of this study was to investigate ADRA2A gene polymorphisms in the Chinese Han population and their association with the cardiovascular response to intravenous dexmedetomidine infusion. Sixty elective surgery patients of Chinese Han nationality were administered 1 μg/kg dexmedetomidine intravenously over 10 min as a premedication. ADRA2A C-1291G and A1780G polymorphism status was determined in these patients, and their relationships to changes in blood pressure and heart rate after dexmedetomidine administration were analyzed. There were neither significant differences in systolic or diastolic blood pressure changes in individuals with different A1780G and C-1291G genotypes after dexmedetomidine administration, nor in heart rates among the different A1780G genotypes. However, there were significant differences in changes in heart rates in patients with different C-1291G genotypes. There were no significant differences in the sedative effects of dexmedetomidine among different A1780G and C-1291G genotypes. Logistic regression revealed that the C-1291G polymorphism was associated with differential decreases in heart rate after intravenous infusion of dexmedetomidine. These findings indicate that the ADRA2A C-1291G polymorphism can affect heart rate changes in patients after in-utravenous infusion of dexmedetomidine.
There are differences in individual cardiovascular responses to the administration of dexmedetomidine, a highly selective α_(2A)-adrenergic receptor(ADRA2A) agonist. The aim of this study was to investigate ADRA2A gene polymorphisms in the Chinese Han population and their association with the cardiovascular response to intravenous dexmedetomidine infusion. Sixty elective surgery patients of Chinese Han nationality were administered 1 μg/kg dexmedetomidine intravenously over 10 min as a premedication. ADRA2A C-1291G and A1780G polymorphism status was determined in these patients, and their relationships to changes in blood pressure and heart rate after dexmedetomidine administration were analyzed. There were neither significant differences in systolic or diastolic blood pressure changes in individuals with different A1780G and C-1291G genotypes after dexmedetomidine administration, nor in heart rates among the different A1780G genotypes. However, there were significant differences in changes in heart rates in patients with different C-1291G genotypes. There were no significant differences in the sedative effects of dexmedetomidine among different A1780G and C-1291G genotypes. Logistic regression revealed that the C-1291G polymorphism was associated with differential decreases in heart rate after intravenous infusion of dexmedetomidine. These findings indicate that the ADRA2A C-1291G polymorphism can affect heart rate changes in patients after in-utravenous infusion of dexmedetomidine.
引文
Galley HF, Mahdy A, Lowes DA, 2005. Pharmacogenetics and anesthesiologists. Pharmacogenomics, 6(8):849-856.https://doi.org/10.2217/14622416.6.8.849
Ice CJ, Personett HA, Frazee EN, et al., 2016. Risk factors for dexmedetomidine-associated hemodynamic instability in noncardiac intensive care unit patients. Anesth Analg,122(2):462-469.https://doi.org/10.1213/ANE.0000000000001125
Kohli U, Muszkat M, Sofowora GG, et al., 2010. Effects of variation in the humanα2A-andα2C-adrenoceptor genes on cognitive tasks and pain perception. Eur J Pain, 14(2):154-159.https://doi.org/10.1016/j.ejpain.2009.04.003
Kohli U, Pandharipande P, Muszkat M, et al., 2012. CYP2A6genetic variation and dexmedetomidine disposition. Eur J Clin Pharmacol, 68(6):937-942.https://doi.org/10.1007/s00228-011-1208-z
Kurnik D, Muszkat M, Li C, et al., 2006. Variations in theα2A-adrenergic receptor gene and their functional effects.Clin Pharmacol Ther, 79(3):173-185.https://doi.org/10.1016/j.clpt.2005.10.006
Kurnik D, Muszkat M, Sofowora GG, et al., 2008. Ethnic and genetic determinants of cardiovascular response to the selectiveα2-adrenoceptor agonist dexmedetomidine. Hypertension, 51(2):406-411.https://doi.org/10.1161/HYPERTENSIONAHA.107.098939
Kurnik D, Muszkat M, Li C, et al., 2011. Genetic variations in theα2A-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine. Circ Cardiovasc Genet, 4(2):179-187.https://doi.org/10.1161/CIRCGENETICS.110.957662
Li TJ, Zhu XL, Wu XP, et al., 2012. Evaluation of the association between the ADRA2A genetic polymorphisms and type 2 diabetes in a Chinese Han population. Genet Test Mol Biomarkers, 16(12):1424-1427.https://doi.org/10.1089/gtmb.2012.0189
Lima JJ, Feng H, Duckworth L, et al., 2007. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism, 56(6):757-765.https://doi.org/10.1016/j.metabol.2007.01.007
Madsen O, Willemsen D, Ursing BM, et al., 2002. Molecular evolution of the mammalian alpha 2B adrenergic receptor.Mol Biol Evol, 19(12):2150-2160.https://doi.org/10.1093/oxfordjournals.molbev.a004040
Mantz J, Josserand J, Hamada S, 2011. Dexmedetomidine:new insights. Eur J Anaesthesiol, 28(1):3-6.https://doi.org/10.1097/EJA.0b013e32833e266d
Neema PK, 2012. Dexmedetomidine in pediatric cardiac anesthesia. Ann Card Anaesth, 15(3):177-179.https://doi.org/10.4103/0971-9784.97972
Paliwal B, Rai P, Kamal M, et al., 2015. Comparison between dexmedetomidine and propofol with validation of bispectral index for sedation in mechanically ventilated intensive care patients. J Clin Diagn Res, 9(7):UC01-UC05.https://doi.org/10.7860/JCDR/2015/14474.6258
Small KM, Brown KM, Seman CA, et al., 2006. Complex haplotypes derived from noncoding polymorphisms of the intronless α2A-adrenergic gene diversify receptor expression. Proc Natl Acad Sci USA, 103(14):5472-5477.https://doi.org/10.1073/pnas.0601345103
Talke P, Lobo E, Brown R, 2003. Systemically administeredα2-agonist-induced peripheral vasoconstriction in humans.Anesthesiology, 99(1):65-70.
Talke P, Stapelfeldt C, Lobo E, et al., 2005. Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.Pharmacogenet Genomics, 15(5):357-363.
Ya?ar S, Yavas S, Karahalil B, 2011. The role of the ADRA2A C1291G genetic polymorphism in response to dexmedetomidine on patients undergoing coronary artery surgery. Mol Biol Rep, 38(5):3383-3389.https://doi.org/10.1007/s11033-010-0446-y
Yin L, Zhang X, Huang Y, et al., 2016. Catecholamine pathway polymorphisms and antidepressant response. Asia Pac Psychiatry, 8(2):109-117.https://doi.org/10.1111/appy.12180
Ice CJ, Personett HA, Frazee EN, et al., 2016. Risk factors for dexmedetomidine-associated hemodynamic instability in noncardiac intensive care unit patients. Anesth Analg,122(2):462-469.https://doi.org/10.1213/ANE.0000000000001125
Kohli U, Muszkat M, Sofowora GG, et al., 2010. Effects of variation in the humanα2A-andα2C-adrenoceptor genes on cognitive tasks and pain perception. Eur J Pain, 14(2):154-159.https://doi.org/10.1016/j.ejpain.2009.04.003
Kohli U, Pandharipande P, Muszkat M, et al., 2012. CYP2A6genetic variation and dexmedetomidine disposition. Eur J Clin Pharmacol, 68(6):937-942.https://doi.org/10.1007/s00228-011-1208-z
Kurnik D, Muszkat M, Li C, et al., 2006. Variations in theα2A-adrenergic receptor gene and their functional effects.Clin Pharmacol Ther, 79(3):173-185.https://doi.org/10.1016/j.clpt.2005.10.006
Kurnik D, Muszkat M, Sofowora GG, et al., 2008. Ethnic and genetic determinants of cardiovascular response to the selectiveα2-adrenoceptor agonist dexmedetomidine. Hypertension, 51(2):406-411.https://doi.org/10.1161/HYPERTENSIONAHA.107.098939
Kurnik D, Muszkat M, Li C, et al., 2011. Genetic variations in theα2A-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine. Circ Cardiovasc Genet, 4(2):179-187.https://doi.org/10.1161/CIRCGENETICS.110.957662
Li TJ, Zhu XL, Wu XP, et al., 2012. Evaluation of the association between the ADRA2A genetic polymorphisms and type 2 diabetes in a Chinese Han population. Genet Test Mol Biomarkers, 16(12):1424-1427.https://doi.org/10.1089/gtmb.2012.0189
Lima JJ, Feng H, Duckworth L, et al., 2007. Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism, 56(6):757-765.https://doi.org/10.1016/j.metabol.2007.01.007
Madsen O, Willemsen D, Ursing BM, et al., 2002. Molecular evolution of the mammalian alpha 2B adrenergic receptor.Mol Biol Evol, 19(12):2150-2160.https://doi.org/10.1093/oxfordjournals.molbev.a004040
Mantz J, Josserand J, Hamada S, 2011. Dexmedetomidine:new insights. Eur J Anaesthesiol, 28(1):3-6.https://doi.org/10.1097/EJA.0b013e32833e266d
Neema PK, 2012. Dexmedetomidine in pediatric cardiac anesthesia. Ann Card Anaesth, 15(3):177-179.https://doi.org/10.4103/0971-9784.97972
Paliwal B, Rai P, Kamal M, et al., 2015. Comparison between dexmedetomidine and propofol with validation of bispectral index for sedation in mechanically ventilated intensive care patients. J Clin Diagn Res, 9(7):UC01-UC05.https://doi.org/10.7860/JCDR/2015/14474.6258
Small KM, Brown KM, Seman CA, et al., 2006. Complex haplotypes derived from noncoding polymorphisms of the intronless α2A-adrenergic gene diversify receptor expression. Proc Natl Acad Sci USA, 103(14):5472-5477.https://doi.org/10.1073/pnas.0601345103
Talke P, Lobo E, Brown R, 2003. Systemically administeredα2-agonist-induced peripheral vasoconstriction in humans.Anesthesiology, 99(1):65-70.
Talke P, Stapelfeldt C, Lobo E, et al., 2005. Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.Pharmacogenet Genomics, 15(5):357-363.
Ya?ar S, Yavas S, Karahalil B, 2011. The role of the ADRA2A C1291G genetic polymorphism in response to dexmedetomidine on patients undergoing coronary artery surgery. Mol Biol Rep, 38(5):3383-3389.https://doi.org/10.1007/s11033-010-0446-y
Yin L, Zhang X, Huang Y, et al., 2016. Catecholamine pathway polymorphisms and antidepressant response. Asia Pac Psychiatry, 8(2):109-117.https://doi.org/10.1111/appy.12180