title: Polymorphism of the Glutamate Transporter Protein EAAT2 and Migraine Transformation into Chronic Daily Headache.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, The Catholic University of Korea College of Medicine, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea.
authors.forename: Hae-Eun
authors.initials: HE
authors.lastname: Shin
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Han
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Lee
authors.forename: Jeong-Wook
authors.initials: JW
authors.lastname: Park
references.citation: Cephalalgia. 2005 Jul;25(7):545-6
references.pmid: 15955043
references.citation: Headache. 2007 Jan;47(1):65-72
references.pmid: 17355496
references.citation: Headache. 2006 Oct;46  Suppl 3:S88-97
references.pmid: 17034403
references.citation: Brain Res Rev. 2009 Apr;60(1):214-25
references.pmid: 19146877
references.citation: J Headache Pain. 2008 Oct;9(5):295-300
references.pmid: 18690491
references.citation: Neurology. 2003 Jul 22;61(2):160-4
references.pmid: 12874392
references.citation: Headache. 2007 Jun;47(6):842-7
references.pmid: 17578532
references.citation: CNS Neurol Disord Drug Targets. 2007 Aug;6(4):251-7
references.pmid: 17691981
references.citation: Pharmacol Ther. 2009 Nov;124(2):168-84
references.pmid: 19615406
references.citation: Headache. 2006 Jun;46 Suppl 1:S39-44
references.pmid: 16927963
references.citation: Headache. 1982 Mar;22(2):66-8
references.pmid: 7085263
references.citation: Mol Psychiatry. 2007 Dec;12(12):1065-78
references.pmid: 17684493
references.citation: Neurol Neurochir Pol. 2006 Mar-Apr;40(2 Suppl 1):S7-41
references.pmid: 16916264
references.citation: Prog Neurobiol. 2001 Sep;65(1):1-105
references.pmid: 11369436
references.citation: Neuroreport. 1997 Feb 10;8(3):775-7
references.pmid: 9106765
references.citation: J Headache Pain. 2010 Oct;11(5):431-5
references.pmid: 20652353
references.citation: Neurology. 2003 Jul 22;61(2):154-5
references.pmid: 12874389
references.citation: Pharmacogenomics. 2008 Feb;9(2):179-94
references.pmid: 18370847
references.citation: Semin Neurol. 2006 Apr;26(2):232-41
references.pmid: 16628534
references.citation: Epilepsy Res. 2000 Aug;41(1):75-81
references.pmid: 10924870
references.citation: Headache. 2006 Oct;46(9):1334-43
references.pmid: 17040331
references.citation: Headache. 2005 Oct;45(9):1229-35
references.pmid: 16178954
references.citation: Neurosci Lett. 2007 Nov 5;427(2):99-102
references.pmid: 17920768
references.citation: Lancet Neurol. 2008 Apr;7(4):354-61
references.pmid: 18339350
references.citation: J Exp Med. 2006 Mar 20;203(3):711-7
references.pmid: 16520390
references.citation: Prog Neurobiol. 1998 Feb;54(3):349-65
references.pmid: 9481803
references.citation: Eur J Neurol. 2006 Sep;13(9):1009-13
references.pmid: 16930369
references.citation: J Neurosci. 1994 Sep;14(9):5559-69
references.pmid: 7521911
references.citation: Neurology. 2009 Feb 3;72(5 Suppl):S8-13
references.pmid: 19188565
references.citation: J Neuroimmunol. 2008 Mar;195(1-2):194-8
references.pmid: 18378006
references.citation: Cephalalgia. 2009 Dec;29 Suppl 3:7-14
references.pmid: 20017749
references.citation: Mol Pain. 2008 Apr 16;4:12
references.pmid: 18416824
references.citation: Cerebrovasc Dis. 2006;21 Suppl 2:1-8
references.pmid: 16651809
references.citation: Cephalalgia. 2004 Sep;24(9):735-9
references.pmid: 15315529
references.citation: Neurology. 2005 Aug 23;65(4):529-34
references.pmid: 16116111
references.citation: Mol Pain. 2009 Jul 01;5:37
references.pmid: 19570226
references.citation: Med Clin North Am. 1999 May;83(3):585-96
references.pmid: 10386116
references.citation: J Physiol. 1982 Jun;327:65-78
references.pmid: 6288930
references.citation: J Headache Pain. 2010 Apr;11(2):151-6
references.pmid: 20213484
references.citation: Cephalalgia. 1999 May;19(4):207-10
references.pmid: 10376164
references.citation: J Neurol. 1999 Dec;246(12):1140-4
references.pmid: 10653305