Patients can be classified into different mitochondrial haplogroups comprising people with the same variations within the genetic material of their mitochondria. The effectiveness of vitamin B2 as a preventive treatment depends on which haplogroup they belong to. (Read the article Migraine: its multiple facets). Vitamin B2 may thus, help to counter the metabolic consequences of certain variations in the mitochondrial genome that increase the susceptibility to migraine.

Glutamate, a key protagonist in migraine with aura

Another aspect of the Headache Research Unit’s work belongs the International Headache Genetics Consortium, involving more than 40 research centres worldwide. Together, the various teams of researchers have succeeded in collecting genetic data from tens of thousands of control subjects and clinically well characterized migraine sufferers.

Scientists are using this gigantic database to uncover the common genetic variants in people with migraine or with a certain type of migraine. In 2010, they were able to pinpoint the first undeniable genetic link in migraine with aura (read the article The first genetic factor for the ‘common’ migraine), found in an intergenic region located on chromosome 8, which codes for a protein expressed within astrocytes, the glial cells responsible for buffering glutamate in the brain. . The protein in question captures and recycles the glutamate released from nerve endings to prevent it from accumulating in the synaptic clefts. An excess of glutamate between neurons can lead to pathological effects such as neuronal hyperexcitability and a phenomenon called “cortical spreading depression” (CSD) that produces the migraine aura. Published in the journal Nature Genetics (2), the results of this study have led the researchers to offer the following hypothesis: the genetic anomaly detected on chromosome 8 can promote impaired glutamate re-uptake and thus cause, between attacks, increased excitability in the brains of migraine sufferers that culminates, during the attack, in CSD ? 

A neurovascular disease

More recently, scientists from the International Headache Genetics Consortium have published a new study in Nature Genetics (3). “More than 500 000 markers were tested in the genome of 5000 migraine sufferers without aura who agreed to give a sample of their DNA for this study. Our team contributed for 10% of these samples and I would like to take this opportunity to thank the patients for their cooperation”, says Jean Schoenen.

This time, the researchers unearthed two genes (MEF2D and TGFBR2) that are significantly involved in migraine without aura, the most widespread form of migraine in the general population. “This study also allowed us to confirm the involvement of two other genes in this form of migraine, LRP1 and TRPM8, discovered by an American team in a previous study on migraine in general”, Jean Schoenen points out. Hence, four genetic regions that play a role in the susceptibility to migraine without aura have now been identified. It is the first time that genetic factors directly and specifically associated with this type of migraine have been detected within the genome.

(2)  Anttila, V., et al. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nature Genetics 2010 ; 42(10):869-73 Epub 2010 Aug 29
(3) Freilinger, T et al. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nature Genetics 2012; 44(7):777-82 Available online at doi: 10.1038/