Genetics of migraine and pharmacogenomics some co

Authors: Maria Piane Patrizia Lulli Ivano Farinelli Simona Simeoni Sergio De Filippis Francesca Romana Patacchioli Paolo Martelletti

Publish Date: 2007/12

Volume: 8, Issue: 6, Pages: 334-

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Abstract

Although family and twin studies show that there is a genetic component in migraine no genes predisposing to common forms of the disorder migraine with and without aura have been identified Patients with migraine respond differently to a given drug administered The efficacy of therapy and the occurrence of adverse drug response are a consequence of individual variability Genetic profiling of predisposition to migraine should facilitate the development of more effective diagnostic and therapeutic applications The development of International Hap Map project could provide a powerful tool for identification of the candidate genes in this complex disease and pharmacogenomics research could be the promise for individualized treatments and prevention of adverse drug responseMigraine is a complex disorder caused by a combination of genetic and environmental factors At present the measure in which these two factors influence each other is unknown It is possible to define this disease as a complex spectrum including features such as craniofacial pain autonomic dysfunctions mood disregulations and spreading cortical disturbance represented by both positive and negative aura phenomena 1–5Migraine diagnosis is based on anamnesis a record patient’s symptomatology and the exclusion of secondary causes A positive familial history often represents further evidence of this diagnosis A more precise determination of familial aggregation appears in the calculation of disease relative risk of the population in specified groups of relatives Epidemiological surveys found that firstdegree relatives of probands displayed a much increased risk of developing the disorder of proband as compared to the general population 5 The risk increase in close relatives obviously does not imply the pathology’s manifestation but only the sharing of a genotypic pattern which determines the outbreak of clinical manifestations after environmental stimuli of different kinds stress factors food smellsAt present the International Headache Society IHS classification recognises some phenotypical features attributing them to diagnostic subtypes However patients with the same diagnosis present a symptomatological pattern type of pain pain location accompanying symptoms underlining a great variability of expressions According to this view migraine could represent a syndrome whose clinical components are the reflection of specific loci expressions independently influencing susceptibility to migraine 6The family aggregation of migraine with aura MA and migraine without aura MO evidence that there is a genetic component as the basis of migraine susceptibility In a Finnish study involving 2690 monozygotic and 5497 dizygotic twin pairs the genetic component ranged from 34 to 51 in different migraine types without remarkable variations with respect to gender Such a concordance emphasises the multifactorial nature of this pathology 7 Similar results have been obtained in several studies on adult twin pairs 8–10Although family and twin studies show that there is a genetic component in migraine no genes predisposing to common forms of the disorder have been identified At present several loci 4q21–q24 5q21 6p122–p211 11q24 14q212–q223 and 15q11–q13 linked to common forms of migraine with evidence of linkage have been reported Several genes were described involved in migraine in many studies but always with controversial results In a more general scenario genetic studies on primary headaches constitute challenges made more complex by this pathologyPatients with migraine and headache respond differently to a given drug administered The efficacy of a drug therapy and the occurrence of adverse reactions are a direct consequence of individual variability Most of this variation in individual response is genetically determined and is the object of the study of pharmacogenetics

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