De Marchis Maria Laura, Barbanti Piero, Palmirotta Raffaele, Egeo Gabriella, Aurilia Cinzia, Fofi Luisa, Piroso Serena, Ialongo Cristiano, Della-Morte David, D'Andrea Giovanni, Ferroni Patrizia, Guadagni Fiorella
Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy,
J Headache Pain. 2015;16:520. doi: 10.1186/s10194-015-0520-x. Epub 2015 Apr 30.
The study of COMT gene polymorphisms in migraine could be of particular interest since impaired catecholaminergic neurotransmission, namely chronic dopaminergic and noradrenergic hypofunction, is a peculiar migraine trait. In this study, for the first time, we focused on the role of COMT rs4818 genetic variant, the polymorphism most strongly affecting COMT activity, in migraine. This study was conducted in a cohort of carefully clinical characterized Caucasian migraineurs recruited in a specifically dedicated migraine biobank, providing also a replication study on rs4680 polymorphism.
Genotyping of rs4680 and rs4818 Catechol-O-Methyltransferase gene polymorphisms was performed on 380 unrelated migraine patients, and 132 healthy subjects matched for age, gender and race-ethnicity, with no clinical evidence or family history of migraine or other neurological diseases. The rs4680 and rs4818 genotypic frequencies did not deviate from those expected for a population in Hardy-Weinberg equilibrium and did not correlate with demographics or clinical migraine features, even when considering migraine subtypes such as dopaminergic migraine, menstrual migraine, and menstrually related migraine .
COMT genotype does not influence migraine susceptibility or phenotype, even considering rs4818 polymorphism and peculiar clinical subtypes. This finding prompts to go over COMT to explain catecholamine derangement in migraine, exploring enzymes involved in catecholamines synthesis and catabolism, such as monoamine-oxidase, dopamine beta-hydroxylase, tyrosine-hydroxylase or tyrosine-decarboxylase, among others.
偏头痛中儿茶酚-O-甲基转移酶（COMT）基因多态性的研究可能特别有意义，因为儿茶酚胺能神经传递受损，即慢性多巴胺能和去甲肾上腺素能功能减退，是偏头痛的一个特殊特征。在本研究中，我们首次聚焦于COMT rs4818基因变异（最强烈影响COMT活性的多态性）在偏头痛中的作用。本研究在一个专门的偏头痛生物样本库中招募的一组经过仔细临床特征描述的白种人偏头痛患者中进行，还对rs4680多态性进行了重复研究。
对380名无亲缘关系的偏头痛患者以及132名年龄、性别和种族匹配的健康受试者进行了rs4680和rs4818儿茶酚-O-甲基转移酶基因多态性的基因分型，这些健康受试者无偏头痛或其他神经系统疾病的临床证据或家族史。rs4680和rs4818的基因型频率与处于哈迪-温伯格平衡的人群预期频率无偏差，且与人口统计学或临床偏头痛特征无关，即使考虑多巴胺能偏头痛、月经性偏头痛和月经相关偏头痛等偏头痛亚型时也是如此。
即使考虑rs4818多态性和特殊临床亚型，COMT基因型也不影响偏头痛易感性或表型。这一发现促使我们超越COMT来解释偏头痛中的儿茶酚胺紊乱，探索参与儿茶酚胺合成和分解代谢的酶，如单胺氧化酶、多巴胺β-羟化酶、酪氨酸羟化酶或酪氨酸脱羧酶等。
