Look beyond Catechol-O-Methyltransferase genotype for cathecolamines derangement in migraine: the BioBIM rs4818 and rs4680 polymorphisms study.

Maria Laura De Marchis,Gabriella Egeo,Cristiano Ialongo,Fiorella Guadagni,Serena Piroso,Luisa Fofi,Piero Barbanti,Patrizia Ferroni,Raffaele Palmirotta,Giovanni D’Andrea,David Della-Morte,Cinzia Aurilia

doi:10.1186/s10194-015-0520-x

Abstract

BackgroundThe 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.FindingsGenotyping 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.ConclusionsCOMT 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.

Highlights

Non-physiological catecholamine levels play a major role in migraine aetiology [1]
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
Populations Three hundred-eighty Mediterranean Caucasian unrelated individuals affected by migraine without aura

Summary

Conclusions

COMT genotype does not influence migraine susceptibility or phenotype, even when considering peculiar clinical subtypes (dopaminergic migraine, HMM). This finding coupled with the well established catecholaminergic imbalance characterizing migraine biotypes prompts to a thorough investigation of other enzymes involved in catecholamines synthesis and catabolism. Authors’ contributions MLDM carried out the molecular genetic studies, participated in the sequence alignment and drafted the manuscript. PB and RP conceived of the study, participated in its design and coordination and helped to draft the manuscript. DDM, GDA, PF and FG conceptualized and designed the study, revised the manuscript and approved the final manuscript as submitted. All authors read and approved the final manuscript

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