They discover genetic evidence of the common migraine

• April 19, 2024

An international consortium of geneticists and researchers specializing in headaches has discovered a genetic variant characteristic of people prone to suffer from a common form of migraine . The study, about which an article has been published in the journal Nature Genetics, received funding from the EUROHEAD project (Genes of migraine and neurobiological routes), financed in turn with 3.2 million euros through the sixth Framework Program (FP6).

There are seven types of migraine, all of them extremely painful. During a migraine attack patients are sensitive to light, sound and often experience nausea, vomiting or temporary loss of vision. This condition is associated with several causes, including stress and the Lack of sleep . Hormonal changes can also cause attacks, with the incidence being higher in women than in men. Specifically, it is estimated that in Europe 8% of men and 17% of women suffer from migraines regularly.

The scientific community learned a few years ago that the susceptibility of an individual depends to a large extent on genetic factors. Recently, several genetic mutations that cause rare and extreme forms of migraines, but genetic factors that underlie the common migraine were not known until now.

The research process

In the referred research, a study of pan-genomic association , scientists from 40 research centers across Europe worked as a team to study genetic data of more than 50 thousand people. In a first phase they compared the genomes of 2,731 migraine patients from Germany, the Netherlands and Finland with those of 10,747 controls. To confirm the results, they compared the genomes of 3,202 patients with those of 40,062 controls. The team discovered that patients with a variant of DNA (specific deoxyribonucleic acid) located on chromosome 8 (between the PGCP and MTDH / AEG-1 genes) were more likely to suffer from migraines.

"This is the first time we have managed to study the genomes of several thousand people and to find genetic clues that clarify the common migraine, "said Dr. Aarno Palotie, director of the International Genetics Consortium for Headache (IHGC). Wellcome Trust Sanger Institute (UK).

The researchers indicated that the genetic variant plays a basic role in the regulation of a neurotransmitter called glutamate . In particular, it is capable of altering the activity of MTDH / AEG-1, which in turn regulates the activity of the EAAT2 gene. The protein EAAT2, which is usually responsible for eliminating glutamate from synapse brain, has already been linked to other neurological diseases such as epilepsy and the schizophrenia .

Author's opinion

The authors understand that the relationship between the variant (called rs1835740) and migraine is based on a poor regulation of the glutamate that could cause an accumulation of this chemical substance in the cerebral synapses, causing the patient to be increasingly sensitive to the factors that cause migraines . They suggest that a possible therapeutic method would be to prevent the accumulation of glutamate.

"Although we know that the EAAT2 gene plays a crucial function In several human neurological processes, and probably in the development of migraine, until now no relationship has been established that suggests that the accumulation of glutamate in the brain could influence the common migraine, "said Professor Christian Kubisch of the University of Ulm (Germany) This research clears the way for the realization of new studies that they treat in depth the biology of the disease and in what way this concrete alteration can exert its effect.

"Studies of this kind are only possible thanks to large-scale international collaborations that gather an abundance of data with adequate capacity and resources to detect this genetic variant. discovery opens new ways to understand human diseases common, "said Dr. Palotie.

The authors warn that it is necessary to deepen the study of this variant of DNA and its effect on the genes that surround it to know the mechanisms that underlie migraine attacks. "This variant only clarifies for a small fraction the genetic variation total that is observed in migraine, "concludes the study.It is expected that future pangenomic association studies will be clarified to a greater extent this variation.

These investigations should also study broader population samples, since the study presented was based on data from people who had attended clinics specialized in headaches . "Since they have gone to a specialized clinic it is likely that they are only the most extreme cases among the population suffering from the common migraine," explained Dr. Gisela Terwindt of the University Medical Center of Leiden (The Netherlands). "In the future associations should be investigated in the general population, in which there will also be less acute cases."

For more information visit:

Wellcome Trust Sanger Institute: //www.sanger.ac.uk/

Nature Genetics: //www.nature.com/ng/index.html

EuroHead: //www.eurohead.org/

© European Union: CORDIS

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