Università del Piemonte Orientale "A. Avogadro," Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Novara, Italy.
J Pain. 2013 Oct;14(10):1097-106. doi: 10.1016/j.jpain.2013.04.006. Epub 2013 Jun 15.
Genetic variation in the COMT gene is thought to have clinical implications for pain perception and pain treatment. In the present study, we first evaluated the association between COMT rs4680 and the analgesic response to intrathecal morphine in patients with chronic low back pain to provide confirmation of previously reported positive findings. Next, we assessed the relationship between rs4680 and headache response to triptans in 2 independent cohorts of migraine patients. In patients with chronic low back pain (n = 74), logistic stepwise regression analysis showed that age (odds ratio [OR]: .90, 95% confidence interval [CI]: .85-.96, P = .002) and the presence of the COMT Met allele (vs Val/Val, OR: .21, 95% CI: .04-.98, P = .048) were predictive factors for lower risk of poor analgesic response to intrathecal morphine. Intriguingly, in migraine patients, the COMT rs4680 polymorphism influenced headache response to triptans in the opposite direction. Indeed, in an exploratory cohort of migraine patients without aura (n = 75), homozygous carriers of the COMT 158Met allele were found at increased risk to be poor responders to frovatriptan when compared to homozygous patients for the Val allele (OR: 5.20, 95% CI: 1.25-21.57, P = .023). In the validation cohort of migraine patients treated with triptans other than frovatriptan (n = 123), logistic stepwise regression analysis showed that use of prophylactic medications (OR: .43, 95% CI: .19-.99, P = .048) and COMT Met/Met genotype (vs Val/Val, OR: 4.29, 95% CI: 1.10-16.71, P = .036) were independent risk factors for poor response to triptans.
This study highlights the importance of COMT rs4680 in influencing the clinical response to drugs used for chronic pain, including opioid analgesics and triptans. These findings also underline a complex relationship between COMT genotypes and pain responder status.
人们认为 COMT 基因的遗传变异对疼痛感知和疼痛治疗具有临床意义。在本研究中，我们首先评估了 COMT rs4680 与慢性腰背痛患者鞘内吗啡镇痛反应之间的关联，以证实先前报道的阳性发现。接下来，我们在 2 个独立的偏头痛患者队列中评估了 rs4680 与曲普坦类药物头痛反应之间的关系。在慢性腰背痛患者（n=74）中，逻辑逐步回归分析显示，年龄（比值比[OR]：0.90，95%置信区间[CI]：0.85-0.96，P=0.002）和 COMT Met 等位基因的存在（与 Val/Val 相比，OR：0.21，95%CI：0.04-0.98，P=0.048）是鞘内吗啡镇痛反应较差的预测因素。有趣的是，在偏头痛患者中，COMT rs4680 多态性对曲普坦类药物头痛反应的影响方向相反。事实上，在无先兆偏头痛患者的探索性队列（n=75）中，与 Val 等位基因纯合子患者相比，COMT 158Met 等位基因纯合子患者发现对 frovatriptan 的反应较差（OR：5.20，95%CI：1.25-21.57，P=0.023）。在接受除 frovatriptan 以外的曲普坦类药物治疗的偏头痛患者验证队列（n=123）中，逻辑逐步回归分析显示，预防性药物的使用（OR：0.43，95%CI：0.19-0.99，P=0.048）和 COMT Met/Met 基因型（与 Val/Val 相比，OR：4.29，95%CI：1.10-16.71，P=0.036）是曲普坦类药物反应不良的独立危险因素。
本研究强调了 COMT rs4680 在影响用于慢性疼痛的药物（包括阿片类镇痛药和曲普坦类药物）临床反应中的重要性。这些发现还强调了 COMT 基因型与疼痛反应者状态之间的复杂关系。
