Migraine Molecular Genetic and Pharmacogenetic Studies

Abstract

Migraine is a painful neurological disease that affects at least 12% of the Australian population. It is generally characterized by recurrent head pain usually accompanied by nausea, vomiting, neurological disturbance, photo-and phonophobia. Migraine has been classified by the international headache society (IHS) into two most common types, migraine with aura (MA) and migraine without aura (MO). The underlying pathophysiology of this debilitating disease is still partially understood and there are no known diagnostic markers for these common types of migraine. Current diagnosis of migraine is based on patient reported symptoms. Studies have shown several health conditions such as epilepsy, depression and stroke to be co-morbid with migraine. Current migraine treatments work with varying efficacy and often have adverse side effects. A greater understanding of this debilitating and painful disease is thus pertinent for developing new and improved migraine treatment. Both familial clustering and twin studies have shown evidence for significant genetic mechanisms to underlie migraine pathogenesis. Migraine is thus currently defined as a complex multifactorial disorder which involves an interaction between genetic and environmental factors. We have not yet identified all migraine genes but a number of genes, causative mutations and susceptibility variants have been identified and are already of significant clinical relevance. Currently the detection of 3 rare subtypes of migraine (Familial Hemiplegic Migraine 1, 2 and 3) and several related conditions with symptom overlap (Episodic Ataxia 2, Spinocerebellar Ataxia Type 6 and Cerebral Autosomal Dominant Arteriopathy with Sub cortical Infarcts and leucoencephalopathy (CADASIL) is undertaken by sequencing, with susceptibility variants for common types of migraine detected by sequencing or genotyping.