Kim Hyungsuk, Lee Hyewon, Rowan Janet, Brahim Jaime, Dionne Raymond A
National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA.
Mol Pain. 2006 Jul 18;2:24. doi: 10.1186/1744-8069-2-24.
Candidate gene studies on the basis of biological hypotheses have been a practical approach to identify relevant genetic variation in complex traits. Based on previous reports and the roles in pain pathways, we have examined the effects of variations of loci in the genes of monoamine neurotransmitter systems including metabolizing enzymes, receptors and transporters on acute clinical pain responses in humans.
Variations in the catecholamine metabolizing enzyme genes (MAOA and COMT) showed significant associations with the maximum post-operative pain rating while the serotonin transporter gene (SLC6A4) showed association with the onset time of post-operative pain. Analgesic onset time after medication was significantly associated with the norepinephrine transporter gene (SLC6A2). However, the association between COMT genetic variation and pain sensitivity in our study differ from previous studies with small sample sizes, population stratification and pain phenotype derived from combining different types of pain stimuli. Correcting for multiple comparisons did not sustain these genetic associations between monoamine neurotransmitter systems and pain sensitivity even in this large and homogeneous sample.
These results suggest that the previously reported associations between genetic polymorphisms in the monoamine neurotransmitter systems and the interindividual variability in pain responses cannot be replicated in a clinically relevant pain phenotype.
基于生物学假设的候选基因研究是识别复杂性状中相关基因变异的一种实用方法。基于先前的报道以及在疼痛通路中的作用，我们研究了单胺神经递质系统基因（包括代谢酶、受体和转运体）中位点变异对人类急性临床疼痛反应的影响。
儿茶酚胺代谢酶基因（MAOA和COMT）的变异与术后疼痛最高评分显著相关，而血清素转运体基因（SLC6A4）与术后疼痛发作时间相关。用药后的镇痛起效时间与去甲肾上腺素转运体基因（SLC6A2）显著相关。然而，我们研究中COMT基因变异与疼痛敏感性之间的关联与先前样本量小、存在人群分层以及疼痛表型源于不同类型疼痛刺激组合的研究不同。即使在这个大的同质样本中，校正多重比较后，单胺神经递质系统与疼痛敏感性之间的这些基因关联也未得到维持。
这些结果表明，先前报道的单胺神经递质系统基因多态性与疼痛反应个体间差异之间的关联，在临床相关疼痛表型中无法复制。
