Tan E-C, Lim E C P, Ocampo C E, Allen J C, Sng B-L, Sia A T
KK Research Centre, KK Women's and Children's Hospital, Singapore.
Duke-NUS Graduate Medical School, Singapore.
Pharmacogenomics J. 2016 Apr;16(2):186-92. doi: 10.1038/tpj.2015.33. Epub 2015 May 12.
Catechol-O-methyltransferase (COMT) gene polymorphisms and haplotypes have been associated with both experimental and clinical pain phenotypes. In this prospective study, we investigated the association of three common polymorphisms with experimentally induced pressure pain, postoperative pain and amount of self-administered morphine in 973 patients who underwent scheduled total hysterectomy. DNA extracted from peripheral blood was genotyped for three COMT polymorphisms by Taqman assay or a PCR-based method. In the overall sample, rs4633 and rs4680 were significantly associated with morphine use, whereas rs4818 was associated with time-averaged pain scores. Statistically significant associations were found between COMT rs4633 and rs4680 genotypes and the amount of morphine self-administered through a patient-controlled analgesia pump. For rs4818, the only statistically significant association was with time-averaged pain scores. Haplotype analysis showed statistically significant association of the low pain sensitivity haplotype with time-averaged pain scores; and average pain sensitivity haplotype with total morphine and weight-adjusted morphine.
儿茶酚-O-甲基转移酶(COMT)基因多态性和单倍型与实验性和临床疼痛表型均有关联。在这项前瞻性研究中,我们调查了973例行择期全子宫切除术患者中三种常见多态性与实验性诱导压力痛、术后疼痛及自我使用吗啡量之间的关联。通过Taqman分析或基于聚合酶链反应(PCR)的方法,对从外周血中提取的DNA进行三种COMT多态性的基因分型。在总体样本中,rs–4633和rs4680与吗啡使用显著相关,而rs4818与时间平均疼痛评分相关。在COMT rs4633和rs4680基因型与通过患者自控镇痛泵自我使用的吗啡量之间发现了具有统计学意义的关联。对于rs4818,唯一具有统计学意义的关联是与时间平均疼痛评分相关。单倍型分析显示,低疼痛敏感性单倍型与时间平均疼痛评分具有统计学意义的关联;平均疼痛敏感性单倍型与总吗啡量及体重调整吗啡量具有统计学意义的关联。