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First Genetic Link to Migraines Found

Monday, August 30, 2010 9:25 AM

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An international scientific team has identified for the first time a genetic risk factor associated with common migraines and say their research could open the way for new treatments to prevent migraine attacks.

Researchers who looked at genetic data from 50,000 people from Finland, Germany, and The Netherlands found that patients with a certain DNA variant affecting regulation of a particular brain chemical have a greater risk of developing migraines.

The results suggest that a buildup of that chemical, called glutamate, may play a role in the mechanism of migraines.

"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 Aarno Palotie, chair of the international headache genetics consortium at the Wellcome Trust Sanger Institute in Britain, which led the study.

Migraine affects around one in six women and one in 12 men, and has been estimated to be the most expensive brain disorder to society in the European Union and the United States.

Not only is migraine painful, it also can be disabling and is often a life-long condition. The World Health Organization ranks it 19th among all causes of "years lived with disability," and family life, social life, and work capacity are negatively affected in almost all migraine sufferers.

Global sales of drugs to treat migraine were around $2.6 billion in 2009, according to analysts at Deutsche Bank. GlaxoSmithKline's Imitrex, Merck's' Maxalt, AstraZeneca's Zomig and Pfizer's Relpax are among leading medicines currently on the market for migraine, but the exact causes of the condition remain unknown.

In a study published in the journal Nature on Sunday, Palotie's team said the particular migraine risk DNA variant they had identified was on chromosome 8 between two genes known as PGCP and MTDH/AEG-1.

Their research showed that it appears to regulate levels of glutamate, a chemical known as a neurotransmitter which transports messages between nerve cells in the brain.

It does this by altering the activity of MTDH/AEG-1 in cells, which regulates the activity of the EAAT2 gene -- a protein responsible for clearing glutamate from brain synapses.

Previous research has found links between EAAT2 and other neurological diseases, including epilepsy, schizophrenia, and various mood and anxiety disorders.

"Until now, no genetic link has been identified to suggest that glutamate accumulation in the brain could play a role in common migraine," Christian Kubisch of University of Ulm in Germany, who also worked on the study, said in a statement.

"This research opens the door for new studies to look in depth at the biology of the disease and how this alteration in particular may exert its effect."

The scientists said further research would be needed into the DNA variant, and into its effect on the genes around it, to find out more about how migraines occur. Further work was also needed to search for other possible genetic links, they said.

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