Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) Nco I alleles

Migraine has a major genetic component. Although most recent scientific studies have focused on the role of 5-hydroxytryptamine and neuropeptides in migraine, dopaminergic systems are also implicated in the pathogenesis. Therefore, the dopamine D2 receptor (DRD2) was analyzed as a candidate gene since antagonists of this receptor have been reported to be effective in the acute treatment of migraine. Individuals with migraine with aura (n = 52) have an increased frequency (0.84) of the DRD2 Nco I C allele (chi-square = 6.47; p < 0.005) compared with control individuals (n = 121; C allele frequency = 0.71). Individuals with migraine without aura (n = 77) showed the same DRD2 T allele frequency(0.70) as the control group. Migraine with aura was present in 27% of the C/C individuals, 16% of the C/T individuals, and 5.2% of the T/T individuals. These data suggest that activation of the DRD2 receptor plays a modifying role in the pathophysiology of migraine with aura. As a result, these data provide a molecular rationale for the documented efficacy of DRD2 antagonists in the treatment of migraine with aura.

[1]  Dennis E Bulman,et al.  Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4 , 1996, Cell.

[2]  C. Allis,et al.  Histone Acetylation and Chromatin Assembly: A Single Escort, Multiple Dances? , 1996, Cell.

[3]  D. Comings,et al.  Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes--DRD2, D beta H, and DAT1. , 1996, American journal of medical genetics.

[4]  S. Peroutka,et al.  Familial hemiplegic migraine, nystagmus, and cerebellar atrophy , 1996, Annals of neurology.

[5]  D. Yealy,et al.  Randomized, placebo-controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache. , 1995, Annals of emergency medicine.

[6]  P. Piccini,et al.  Transcranial Doppler Ultrasound in Migraine and Tension-Type Headache After Apomorphine Administration: Double-Blind Crossover Versus Placebo Study , 1995, Cephalalgia : an international journal of headache.

[7]  J. Tajti,et al.  Neuropeptides and Migraine: The Role of CGRP , 1995 .

[8]  C. Weiller,et al.  Brain stem activation in spontaneous human migraine attacks , 1995, Nature Medicine.

[9]  D. Comings,et al.  Dopamine D2 receptor gene (DRD2) haplotypes and the defense style questionnaire in substance abuse, Tourette syndrome, and controls , 1995, Biological Psychiatry.

[10]  M. Zompo,et al.  Dopamine Hypersensitivity in Migraine: Role in Apomorphine Syncope , 1995, Headache.

[11]  K. Syndulko,et al.  D2 dopamine receptor TaqI A alleles in medically ill alcoholic and nonalcoholic patients. , 1994, Alcohol and alcoholism.

[12]  R. Fukuda,et al.  Mismatch PCR RFLP detection of DRD2 Ser311Cys polymorphism and schizophrenia. , 1994, Biochemical and biophysical research communications.

[13]  R. Ophoff,et al.  Genetic heterogeneity of familial hemiplegic migraine. , 1994, Genomics.

[14]  M. Itokawa,et al.  Association of dopamine D2 receptor molecular variant with schizophrenia , 1994, The Lancet.

[15]  K. Blum,et al.  No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis. , 1994, JAMA.

[16]  M. McPherson,et al.  Cystic fibrosis gene and mucin secretion , 1994, The Lancet.

[17]  M. Gheorghiade,et al.  WITHDRAWAL OF DIGOXIN FROM PATIENTS WITH CHRONIC HEART FAILURE TREATED WITH ANGIOTENSIN CONVERTING ENZYME INHIBITORS , 2010 .

[18]  M. Itokawa,et al.  A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys). , 1993, Biochemical and biophysical research communications.

[19]  K. Welch,et al.  Drug therapy of migraine. , 1993, The New England journal of medicine.

[20]  C. Deber,et al.  Mutagenesis of bacteriophage IKe major coat protein transmembrane domain: role of an interfacial proline residue. , 1993, Biochemical and biophysical research communications.

[21]  E P Noble,et al.  Allelic association of the D2 dopamine receptor gene with cocaine dependence. , 1993, Drug and alcohol dependence.

[22]  J. Weissenbach,et al.  A gene for familial hemiplegic migraine maps to chromosome 19 , 1993, Nature Genetics.

[23]  L. Stovner,et al.  The IHS Classification For Common Migraine. Is It Ideal? , 1993, Headache.

[24]  J. Hilden,et al.  Familial occurrence of migraine without aura and migraine with aura , 1993, Neurology.

[25]  R. Lipton,et al.  Migraine headache: Epidemiology and health care utilization , 1993, Cephalalgia : an international journal of headache.

[26]  E. MacGregor,et al.  Domperidone Plus Paracetamol in The Treatment of Migraine , 1993, Cephalalgia : an international journal of headache.

[27]  M. Abbar,et al.  D2 dopamine receptor gene and alcoholism. , 1993, Journal of psychiatric research.

[28]  K. Blum,et al.  Substance abuse vulnerability and D2 receptor genes , 1993, Trends in Neurosciences.

[29]  G. L. Ellis,et al.  The efficacy of metoclopramide in the treatment of migraine headache. , 1993, Annals of emergency medicine.

[30]  R. Penn,et al.  Neurosurgical horizons in Parkinson's disease , 1993, Neurology.

[31]  R. Crowe,et al.  Alcoholism and the D2 receptor gene. , 1992, Alcoholism, clinical and experimental research.

[32]  J. Palacios,et al.  Visualization of dopamine D1, D2 and D3 receptor mRNA's in human and rat brain , 1992, Neurochemistry International.

[33]  J. Kelsoe,et al.  Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism , 1992, Biological Psychiatry.

[34]  P Kocsis,et al.  The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. , 1991, JAMA.

[35]  D. Grandy,et al.  Direct sequencing of the dopamine D2 receptor (DRD2) in schizophrenics reveals three polymorphisms but no structural change in the receptor. , 1991, Genomics.

[36]  K. Blum,et al.  Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism. , 1991, Alcohol.

[37]  C. Robert Cloninger,et al.  Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage. , 1991, Archives of general psychiatry.

[38]  E P Noble,et al.  Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. , 1991, Archives of general psychiatry.

[39]  C. Ambrosio,et al.  Interaction of flunarizine with dopamine D2 and D1 receptors. , 1991, European journal of pharmacology.

[40]  O. Blin,et al.  Apomorphine-induced yawning in migraine patients: enhanced responsiveness. , 1991, Clinical neuropharmacology.

[41]  D. Goldman,et al.  Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. , 1990, JAMA.

[42]  C. Allen,et al.  A prospective, double-blind study of metoclopramide hydrochloride for the control of migraine in the emergency department. , 1990, Annals of emergency medicine.

[43]  A. Shuaib,et al.  A comparative trial of three agents in the treatment of acute migraine headache. , 1990, Annals of emergency medicine.

[44]  S. Ed.  The history of veterinary medicine in Alabama, 1892-1952. , 1990 .

[45]  O. Rascol,et al.  Migraine attacks induced by subcutaneous apomorphine in two migrainous parkinsonian patients. , 1990, Clinical neuropharmacology.

[46]  K. Blum,et al.  Allelic association of human dopamine D2 receptor gene in alcoholism. , 1990, JAMA.

[47]  V. Pfaffenrath,et al.  Flunarizine (10 and 20 mg) i.v. Versus Placebo in the Treatment of Acute Migraine Attacks: A Multi-Centre Double-Blind Study , 1990, Cephalalgia : an international journal of headache.

[48]  P. Piccini,et al.  Possible Involvement of Dopaminergic Mechanisms in the Antimigraine Action of Flunarizine , 1990, Cephalalgia : an international journal of headache.

[49]  W. F. Watkins.  Randomized double-blind trial of intravenous prochlorperazine for the treatment of acute headache , 1989 .

[50]  C. Damase-Michel,et al.  Apomorphine potentiates vagal bradycardia. , 1989, European journal of pharmacology.

[51]  P. Lane,et al.  Comparative efficacy of chlorpromazine and meperidine with dimenhydrinate in migraine headache. , 1989, Annals of emergency medicine.

[52]  D. Soyka,et al.  Flunarizine I.V. in the Acute Treatment of Common or Classical Migraine Attacks A Placebo‐Controlled Double Blind Trial , 1989, Headache.

[53]  H. M. O'Connor,et al.  Treatment of migraine with intramuscular chlorpromazine. , 1987, Annals of emergency medicine.

[54]  Sara Romero,et al.  PARKINSONISM, TARDIVE DYSKINESIA, AKATHISIA, AND DEPRESSION INDUCED BY FLUNARIZINE , 1986, The Lancet.

[55]  M. Devoto,et al.  Segregation Analysis of Migraine in 128 Families , 1986, Cephalalgia : an international journal of headache.

[56]  G. Sances,et al.  Changes in the Dopaminergic Control of Prolactin Secretion and in Ovarian Steroids in Migraine , 1986, Cephalalgia : an international journal of headache.

[57]  J. Kurtzke,et al.  On national needs for neurologists in the United States , 1986, Neurology.

[58]  A. Rascol,et al.  Does the Piribedil Test Permit Predicting the Efficacy of Domperidone, a Dopaminergic Antagonist, in the Treatment of Migraine? , 1985, Headache.

[59]  R. Ross,et al.  Intravenous Chlorpromazine ‐ Preliminary Results In Acute Migraine , 1985, Headache.

[60]  J. Mcculloch,et al.  Vasomotor responses of cerebral arterioles in situ to putative dopamine receptor agonists , 1985, British journal of pharmacology.

[61]  J Waelkens,et al.  Dopamine Blockade With Domperidone: Bridge Between Prophylactic and Abortive Treatment of Migraine? A Dose-Finding Study , 1984, Cephalalgia : an international journal of headache.

[62]  K. Iserson.  Parenteral chlorpromazine treatment of migraine. , 1983, Annals of emergency medicine.

[63]  P. Dupui,et al.  Clinical Value of a Dopaminergic Agonist Administration in Migraine Patients , 1983, Headache.

[64]  W. Amery,et al.  Flunarizine, a Calcium Channel Blocker: a New Prophylactic Drug in Migraine , 1983, Headache.

[65]  M. Wilkinson.  Treatment of the Acute Migraine Attack Current Status , 1983, Cephalalgia : an international journal of headache.

[66]  O. Sjaastad.  The International Headache Society. A New Multi-Disciplinary Forum , 1983, Cephalalgia : an international journal of headache.

[67]  J. Waelkens.  Domperidone in the prevention of complete classical migraine. , 1982, British medical journal.

[68]  P. Drury,et al.  Experience with selective venous sampling in diagnosis of ACTH-dependent Cushing's syndrome. , 1982, British medical journal.

[69]  H. Hakkarainen,et al.  Ergotamine vs. Metoclopramide vs. Their Combination in Acute Migraine Attacks , 1982, Headache.

[70]  P. Louis.  A Double‐blind Placebo‐controlled Prophylactic Study of Flunarizine (Sibelium®) in Migraine , 1981, Headache.

[71]  R. Sercombe,et al.  Relaxation by dopaminergic agonists in cerebral and peripheral arteries (in vitro). , 1981, Archives internationales de pharmacodynamie et de therapie.

[72]  N. Raskin.  Pharmacology of migraine. , 1981, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[73]  P. Seeman.  Brain dopamine receptors. , 1980, Pharmacological reviews.

[74]  M. Fanciullacci,et al.  Hyperresponsiveness of Migraine Patients to the Hypotensive Action of Bromocriptine , 1980, Headache.

[75]  T. Moore,et al.  Immunoglobulin, Complement, and Immune Complex Levels During a Migraine Attack , 1980, Headache.

[76]  I. Shoulson,et al.  Bromocriptine inhibits norepinephrine release , 1979, Clinical pharmacology and therapeutics.

[77]  METOCLOPRAMIDE IN MIGRAINE TREATMENT , 1977 .

[78]  F. Sicuteri.  Dopamine, the Second Putative Protagonist in Headache , 1977, Headache.

[79]  W. Allan.  THE INHERITANCE OF MIGRAINE , 1928 .

[80]  H. Fisher.  A new approach to emergency department therapy of migraine headache with intravenous haloperidol: a case series. , 1995, The Journal of emergency medicine.

[81]  S. Colucciello,et al.  Misdiagnosis of appendicitis in nonpregnant women of childbearing age. , 1995, The Journal of emergency medicine.

[82]  K. Blum,et al.  Genetic predisposition in alcoholism: association of the D2 dopamine receptor TaqI B1 RFLP with severe alcoholics. , 1993, Alcohol.

[83]  L. Becker.  Methodology in Cardiac Arrest Research Symposium , 1993 .

[84]  M. Moskowitz.  Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. , 1992, Trends in pharmacological sciences.

[85]  C. Otto,et al.  The role of bicarbonate and fluid loading in improving resuscitation from prolonged cardiac arrest with rapid manual chest compression CPR. , 1990, Annals of emergency medicine.

[86]  A. Lugaresi,et al.  Extrapyramidal syndrome and depression induced by flunarizine. , 1988, European neurology.

[87]  P. Dupui,et al.  Pharmacological exploration of dopamine hypersensitivity in migraine patients. , 1986, International journal of clinical pharmacology research.

[88]  M. Boccuni,et al.  A new nonvascular interpretation of syncopal migraine. , 1982, Advances in neurology.

[89]  Friedman Ap.  Overview of migraine. , 1982 .

[90]  D. Bourne,et al.  Effects of hypothermia on propranolol kinetics. , 1979, Clinical pharmacology and therapeutics.

[91]  B. J. Clark,et al.  Cardiovascular actions of bromocriptine. , 1978, Acta endocrinologica. Supplementum.

[92]  S. Matts.  Metoclopramide in the treatment of migraine. , 1974, The Practitioner.

[93]  K. Heathfield.  Drug treatment of migraine. , 1961, Current medicine and drugs.