Polymorphism of the Glutamate Transporter Protein EAAT2 and Migraine Transformation into Chronic Daily Headache
- PMID: 22087208
- PMCID: PMC3212600
- DOI: 10.3988/jcn.2011.7.3.143
Polymorphism of the Glutamate Transporter Protein EAAT2 and Migraine Transformation into Chronic Daily Headache
Abstract
Background and purpose: The progression of migraine into chronic daily headache involves multiple risk factors, but the main contributor is not known. Glutamate is the major excitatory neurotransmitter in central sensitization, which is an important process in the pathogenesis of migraine transformation. The glutamate transporter protein excitatory amino acid transporter 2 (EAAT2) is the primary modulator of glutamatergic neurotransmission, and genetic polymorphisms of its gene, EEAT2, have been identified. The aim of this study was to determine the effect of EAAT2 polymorphisms on migraine transformation into chronic daily headache.
Methods: We included 74 migraine patients with episodic attack (M-E) and 59 migraine patients with chronic daily headache (M-CDH). After amplifying EAAT2 by polymerase chain reaction, we assessed its genotype frequencies based on restriction fragment length polymorphisms. We reclassified all migraine patients into two groups according to their EAAT2 genotype, either with the A allele (n=62) or without it (n=71), and compared the clinical variables between the two groups.
Results: The genotype frequencies of EAAT2 polymorphisms did not differ between the M-E and M-CDH groups. Comparison between EEAT2 genotypes revealed that the frequency of analgesic usage was significantly higher among migraine patients with the A allele (12.9±1.6 days/month) than in those without the A allele (8.1±1.2 days/month; p=0.019). The other clinical variables of migraine did not differ between the two groups.
Conclusions: The results suggest that EEAT2 polymorphism contributes to the tendency toward frequent analgesic usage in migraine patients. This implies a potential genetic influence on the progression of migraine into chronic daily headache through the development of medication-overuse headache.
Keywords: chronic daily headache; glutamate transporter protein; migraine; polymorphism.
Conflict of interest statement
The authors have no financial conflicts of interest.
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References
-
- Mathew NT, Stubits E, Nigam MP. Transformation of episodic migraine into daily headache: analysis of factors. Headache. 1982;22:66–68. - PubMed
-
- Jensen R, Stovner LJ. Epidemiology and comorbidity of headache. Lancet Neurol. 2008;7:354–361. - PubMed
-
- Zwart JA, Dyb G, Hagen K, Svebak S, Holmen J. Analgesic use: a predictor of chronic pain and medication overuse headache: the Head-HUNT Study. Neurology. 2003;61:160–164. - PubMed
-
- Lipton RB, Bigal ME. Chronic daily headache: is analgesic overuse a cause or a consequence? Neurology. 2003;61:154–155. - PubMed
-
- Russell MB, Ostergaard S, Bendtsen L, Olesen J. Familial occurrence of chronic tension-type headache. Cephalalgia. 1999;19:207–210. - PubMed
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