Genetic link to migraine `identified`

Last Updated: Monday, August 30, 2010 - 00:00

London: Scientists have identified the first-ever genetic risk factor associated with common types of migraine, a finding they claim may soon pave the way for novel therapies to prevent the debilitating pain attacks.

An international team looked at the genetic data of over 50,000 people and found that patients with a particular DNA variant on Chromosome 8 between two genes -- PGCP and MTDH /AEG-1 -- have a greater risk for developing migraine.

The scientists also discovered a potential explanation for this link -- the associated DNA variant regulates levels of glutamatem 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, according to the
`Health and Medicine` journal.

Dr Aarno Palotie of Wellcome Trust Sanger Institute, which spearheaded the study, said: "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.

"Studies of this kind are possible only through largescale international collaboration -- bringing together the wealth of data with the right expertise and resources -- so that we could pick out this genetic variant. This discovery opens new doors to understand common diseases."

In fact, the scientists carried out what is known as a genome-wide association study to zoom in on genome variants that could increase susceptibility to migraine.

The team compared the genomes of more than 3000 people from Finland, Germany and The Netherlands with migraine with the genomes of more than 10,000 non-migraineurs, recruited from pre-existing studies, to spot differences that might account for one group`s increased susceptibility to migraine.

To confirm their 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, say the scientists.

"Although we knew that the EAAT2 gene has a crucial role to play in neurological processes in human and potentially in the development of migraine, until now, no
genetic link has been identified to suggest that glutamate accumulation in brain could play a role in common migraine.

"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," said co-author Christian
Kubisch of Ulm University.

PTI



First Published: Monday, August 30, 2010 - 00:00

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