Fu Zhimei, Hu Bingwei, Ma Tingting, Wang Qiandong, Wang Dongdong
Department of Anesthesiology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
Exp Ther Med. 2020 Apr;19(4):2415-2426. doi: 10.3892/etm.2020.8481. Epub 2020 Jan 31.
It is well known that differences in drug reactions among individuals are widespread, and therefore the study of genetic polymorphisms of drug targets has become a research hotspot. Dexmedetomidine is clinically effective by acting on α2 adrenergic receptor and the impact of the adrenoceptor α2A gene (ADRA2A) polymorphisms on the anesthetic and analgesic effects of dexmedetomidine is related to the clinical application of dexmedetomidine. The present study aimed to analyze the effects of the rs1800035, rs201376588 and rs775887911 locus single-nucleotide polymorphisms of the ADRA2A on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women. A total of 434 Chinese women undergoing cesarean section were enrolled in this study. A 3-ml fasting venous blood sample was collected from all subjects for genomic DNA extraction and genotype detection. The pre-anesthetic and post-anesthetic pain threshold (PTh), pain tolerance threshold (PTTh), mean arterial pressure, heart rate, blood oxygen saturation, cortisol (Cor) content, blood glucose (Glu) content, opioid usage, patient-controlled analgesia pressing times, surgical satisfaction and postoperative adverse reactions were recorded. The visual analogue scale (VAS) and Ramsay sedation score were evaluated. PTh and PTTh in the wild-type women were higher than those in the women with mutations (P<0.05). The postoperative VAS scores of wild-type women were lower than those of mutants (P<0.05). The Ramsay sedation scores of wild-type patients at 12 h after the operation were significantly higher than in those with mutations (P<0.05). The levels of Cor and Glu in women with mutations were significantly higher than those of wild-type women at 12, 24 and 48 h after surgery (P<0.05). The satisfaction with surgery of wild-type patients was higher than that of patients with mutations (P<0.05). Gene mutations of rs1800035, rs201376588 and rs775887911 loci in the ADRA2A gene reduced the anesthetic and analgesic effect during and after cesarean section in Chinese Han women. Postoperative analgesia of mothers with mutations may require higher doses of analgesics.
众所周知，个体间药物反应的差异普遍存在，因此药物靶点基因多态性的研究已成为一个研究热点。右美托咪定通过作用于α2肾上腺素能受体发挥临床疗效，肾上腺素能受体α2A基因（ADRA2A）多态性对右美托咪定麻醉和镇痛效果的影响与右美托咪定的临床应用相关。本研究旨在分析ADRA2A基因的rs1800035、rs201376588和rs775887911位点单核苷酸多态性对中国汉族女性右美托咪定麻醉和镇痛效果的影响。本研究共纳入434例行剖宫产术的中国女性。采集所有受试者3ml空腹静脉血样本用于基因组DNA提取和基因型检测。记录麻醉前和麻醉后疼痛阈值（PTh）、疼痛耐受阈值（PTTh）、平均动脉压、心率、血氧饱和度、皮质醇（Cor）含量、血糖（Glu）含量、阿片类药物用量、患者自控镇痛按压次数、手术满意度和术后不良反应。评估视觉模拟评分（VAS）和 Ramsay镇静评分。野生型女性的PTh和PTTh高于突变型女性（P<0.05）。野生型女性术后VAS评分低于突变型女性（P<0.05）。野生型患者术后12小时的Ramsay镇静评分显著高于突变型患者（P<0.05）。术后12、24和48小时，突变型女性的Cor和Glu水平显著高于野生型女性（P<0.05）。野生型患者对手术的满意度高于突变型患者（P<0.05）。ADRA2A基因rs1800035、rs201376588和rs775887911位点的基因突变降低了中国汉族女性剖宫产术中及术后的麻醉和镇痛效果。突变母亲的术后镇痛可能需要更高剂量的镇痛药。
