Association Between Migraine and the G1246A Polymorphism in the Hypocretin Receptor 2 Gene


  • Markus Schürks MD,

  • Volker Limmroth MD,

  • Ingrid Geissler,

  • Grietje Tessmann,

  • Irini Savidou MD,

  • Jörg Engelbergs PhD,

  • Tobias Kurth MD, ScD,

  • Hans-Christoph Diener MD,

  • Dieter Rosskopf MD

  • From the Department of Neurology, University of Duisburg-Essen, Essen, Germany (Drs. Schürks, Limmroth, Savidou, Engelbergs, and Diener); Department of Neurology, Cologne-City-Hospitals, Cologne, Germany (Dr. Limmroth); Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA (Dr. Kurth); Institute of Pharmacology, Research Center of Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (Drs. Geissler, Tessmann, and Rosskopf).

Address all correspondence to Dr. Markus Schürks, Department of Neurology, University Hospital Essen. Hufelandstrasse 55, 45122 Essen, Germany.


Background.—The hypocretin receptor 2 (HCRTR2) G1246A polymorphism has been associated with the risk for cluster headache. Since the hypothalamic hypocretin/orexin system projects throughout the nervous system and affects multiple vegetative functions including generation of rhythmicity, vasomotion, autonomic symptoms as well as modulation of nociception, it may also be linked with migraine.

Objective.—We thus sought to evaluate whether the HCRTR2 G1246A polymorphism is associated with the risk for migraine.

Methods.—We prospectively established a cohort of 146 unrelated patients with migraine. The control group consisted of 279 healthy volunteers. We genotyped patients and controls for the HCRTR2 G1246A polymorphism and examined an association with presence or absence of migraine.

Results.—Genotype and allele frequencies were not significantly different between migraine patients and controls (genotype distribution: χ2= 4.13, 2 df, P= .13; allele distribution: χ2= 0.9, 1 df, P= .34).

Conclusion.—Our study does not support a major contribution of the HCRTR2 G1246A polymorphism to the pathogenesis of migraine in contrast to its effects in cluster headache.