Finding the Gene for Migraines

Migraine headaches affect 1 in 6 women and 1 in 12 men, and can be triggered by any number of seemingly innocuous events, from eating cheese, to taking birth control pills, to exercising. In 2009, people worldwide spent $2.6 billion on preventative drugs, trying treatments from beta-blockers to anticonvulsants. Yet, despite being considered the most expensive brain disorder in the European Union and United States, the source of migraines has remained elusive . . . until now.

In a collaboration of more than 40 centers around the world led by the International Headache Genetics Consortium, researchers have linked migraine susceptibility to a genetic variant on chromosome 8. By examining 6,000 migraine patients and 50,000 people without migraines, the researchers found that 26% of migraine sufferers possessed a chromosomal variant that appears to alter the activity of genes responsible for the production of excitatory amino acid transporter (EAAT2)—a protein that clears glutamate (a neurotransmitter) from synapses in the brain.

EAAT2 dysregulation has already been implicated in a variety of psychiatric and neurological disorders. Because glutamate is toxic if not cleared efficiently from synapses (as in conditions such as Amyotrophic Lateral Sclerosis), its buildup between nerve endings in the brain could trigger migraines’ painful symptoms, although more research is needed to determine such a cause-effect relationship. Understanding and learning to regulate EAAT2 may be the answer for migraine sufferers, and perhaps Alzheimer, Huntington’s, and ALS patients, as well.

1 Silberstein, S. (2008). Treatment recommendations for migraine Nature Clinical Practice Neurology, 4 (9), 482-489 DOI: 10.1038/ncpneuro0861

2 The International Headache Genetics Consortium et al. (2010). Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1 Nature Genetics DOI: 10.1038/ng.652

3 Pow DV, & Cook DG (2009). Neuronal expression of splice variants of “glial” glutamate transporters in brains afflicted by Alzheimer’s disease: unmasking an intrinsic neuronal property. Neurochemical research, 34 (10), 1748-57 PMID: 19319679

4 Hassel, B., Tessler, S., Faull, R., & Emson, P. (2007). Glutamate Uptake is Reduced in Prefrontal Cortex in Huntington’s Disease Neurochemical Research, 33 (2), 232-237 DOI: 10.1007/s11064-007-9463-1

5 Boston-Howes, W. (2006). Caspase-3 Cleaves and Inactivates the Glutamate Transporter EAAT2 Journal of Biological Chemistry, 281 (20), 14076-14084 DOI: 10.1074/jbc.M600653200

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