Scientists have discovered genes that may be behind migraines, “opening the door to a cure”, reported the Daily Mirror. The newspaper said that these genes normally control the levels of a brain chemical called glutamate, but a variant form of the gene may lead to a build-up of glutamate within the nerve cells. According to the paper, halting this build-up could help stop migraines.
The study behind this story scanned the DNA of several thousand people with and without a history of migraine. It compared their genetics and identified a particular gene variant that was more common in migraine sufferers. The study adds to our understanding of the complex processes that lead to migraines and highlights that there may be genetic causes.
This is important research, but finding genes that are linked to a condition is very different from developing a safe treatment based on this knowledge. Overall, it is premature for newspapers to suggest that this research may soon produce a cure for migraines. Migraine is a complex condition in which the interaction between genes and the environment is likely to be important, meaning there may not be a single cause or cure.
The team found that patients with a particular DNA variant on chromosome 8 have a significantly greater risk for developing migraine. It appears that the associated DNA variant regulates levels of glutamate – a chemical, known as a neurotransmitter, which transports messages between nerve cells in the brain.
The results suggest that an accumulation of glutamate in nerve-cell junctions (synapses) in the brain may play a key role in the initiation of migraine attacks. Prevention of the build-up of glutamate at the synapse may provide a promising target for novel therapeutics to ease the burden of the disease.
Migraine affects approximately one in six women and one in 12 men, and has been estimated to be the most expensive brain disorder to society in Europe and the USA. A US report measures its economic costs as similar to those of diabetes and WHO lists it as one of the top 20 diseases with years lived with disability.
“This is the first time we have been able to peer into the genomes of many thousands of people and find genetic clues to understand common migraine,” said Dr Aarno Palotie, Chair of the International Headache Genetics Consortium at the Wellcome Trust Sanger Institute, which spearheaded the study.
The team carried out a genome-wide association study to identify differences that might account for an individual’s increased susceptibility to migraine. They compared the genomes of more than 3000 people from Finland, Germany and The Netherlands with migraine with the genomes of more than 10 000 people who do not suffer from the condition, recruited from pre-existing studies. To confirm the link, the team compared the genomes of a second group of more than 3000 patients with more than 40 000 apparently healthy people.
The statistical analysis revealed that a DNA variation found between the PGCP and MTDH/AEG-1 genes on chromosome 8 appears to be associated with increased susceptibility to common migraine. The variant appears to alter the activity of MTDH/AEG-1 in cells, which regulates the activity of the EAAT2 gene: the EAAT2 protein is responsible for clearing glutamate from brain synapses in the brain. EAAT2 has previously been linked with other neurological diseases, including epilepsy, schizophrenia, and various mood and anxiety disorders.
