SLC6A2基因多态性与儿童右美托咪定疗效的相关性研究  

Relationship between SLC6A2 gene polymorphism and dexmedetomidine efficacy in pediatric patients

作　　者：蔡馨梅 李碧莲 管宴萍 黄民[1] 宋兴荣[2] 钟国平[1] CAI Xin-mei;LI Bi-lian;GUAN Yan-ping;HUANG Min;SONG Xing-rong;ZHONG Guo-ping(Institute of Clinical Pharmacology,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510080,Guangdong Province,China;Department of Anaesthesiology,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 510120,Guangdong Province,China;Department of Pharmacy,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510220,Guangdong Province,China)

机构地区：[1]中山大学药学院临床药理研究所,广东广州510080 [2]广州医科大学广州市妇女儿童医疗中心麻醉科,广东广州510120 [3]中山大学孙逸仙纪念医院药学部,广东广州510220

出　　处：《中国临床药理学杂志》2021年第10期1146-1149,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家重大科技专项“重大新药创制”资助项目(2020ZX09201021);国家自然科学基金资助项目(81901385);广东省医学科学技术研究基金资助项目(A2019367);广州市妇女儿童医疗中心/广州儿科研究所内部基金资助项目(Pre-PI-2019-011)。

摘　　要：目的探讨去甲肾上腺素转运体基因(SLC6A2)多态性对患儿右美托咪定疗效及药物不良反应的影响。方法纳入239例术前使用右美托咪定麻醉的患儿,用Agena MassARRAY?方法检测患者SLC6A24个单核苷酸多态性(SNP)基因型(rs36006、rs40615、rs42460和rs168924)。用SPSS 25.0软件分析SLC6A2基因多态性与右美托咪定镇静效果、药物不良反应的相关性。结果对于SLC6A2 rs36006,CC基因型携带者相对于TC+TT携带者更易出现镇静失败(50.00%vs 12.21%,P<0.05)。相比于rs40615 TA+TT基因型,AA携带者更容易镇静失败(42.86%vs 11.64%,P<0.05)。rs42460、rs168924与右美托咪定镇静疗效无显著相关性。4个SNP与右美托咪定引起的低血压均无显著相关性(均P>0.05)。多因素Logistic回归方程纳入了SLC6A2 rs36006,其CC基因型是接受右美托咪定的患者镇静失败的危险因素(比值比=11.33,P<0.01)。结论SLC6A2 rs36006和rs40615基因多态性与右美托咪定镇静疗效有关,有可能作为预测右美托咪定疗效的生物标记物。Objective To investigate the effect of norepinephrine transporter gene(SLC6A2) polymorphisms on the sedation efficacy and adverse drug reactions of dexmedetomidine in pediatric patients. Methods A total of 239 pediatric patients receiving dexmedetomidine for pre-operative sedation were recruited in the study. Four single nucleotide polymorphisms(SNPs) of SLC6A2(rs36006, rs40615, rs42460, rs168924) were genotyped using the Agena MassARRAY?. The relationships between SLC6A2 gene polymorphisms and sedation efficacy/adverse effects were analyzed using SPSS 25.0 software. Results SLC6A2 rs36006 CC carriers were more likely to have sedation failure than TC+TT carriers(50.00% vs 12.21%, P<0.05). Compared with rs40615 TA+TT carriers, AA carriers were more prone to fail sedation(42.86% vs 11.64%, P<0.05). No significant relationship was found between rs42460/rs168924 and dexmedetomidine efficacy(P>0.05). There was also no significant association between these SNPs and hypotension caused by dexmedetomidine(P>0.05). Multivariate logistic regression analysis demonstrated that SLC6A2 rs36006 CC genotype was a risk factor for sedation failure among patients receiving dexmedetomidine( odds radio = 11. 33,P < 0. 01). Conclusion SLC6 A2 rs36006 and rs40615 polymorphism could be associated with the efficacy of dexmedetomidine, making them biomarkers that can predict the efficacy of dexmedetomidine.

关 键 词：右美托咪定 基因多态性 去甲肾上腺素转运体基因 药效学 儿童群体 

分 类 号：R971.2[医药卫生—药品]