MTHFR 677C>T Polymorphism and Cluster Headache

Authors

  • Markus Schürks MD, MSc,

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Franziska A. Neumann,

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Christof Kessler MD,

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Hans-Christoph Diener MD,

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Heyo K. Kroemer PhD,

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Tobias Kurth MD, ScD,

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Henry Völzke MD,

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Dieter Rosskopf MD

    1. From the Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA (M. Schürks and T. Kurth); Department of Neurology, University Hospital Essen, Germany (M. Schürks and H.-C. Diener); Department of Neurology, Ernst-Moritz-Arndt-University Greifswald, Germany (F.A. Neumann and C. Kessler); Institute of Pharmacology, Center for Pharmacology and Experimental Therapeutics, University Hospital, Ernst-Moritz-Arndt University, Greifswald, Germany (F.A. Neumann, H.K. Kroemer, and D. Rosskopf); INSERM Unit 708 – Neuroepidemiology, Paris, France (T. Kurth); Faculty of Medicine, Pierre et Marie Curie University, Paris, France (T. Kurth); Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Germany (H. Völzke).
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  • Funding and Support: The Study of Health in Pomerania (SHIP) is funded by grants from the German Federal Ministry of Education and Research (BMBF 01ZZ96030) and from the Ministry for Education, Research and Cultural Affairs and the Ministry for Social Affairs of the Federal State of Mecklenburg-Vorpommern.

  • Disclosures: Dr. Schürks has received investigator-initiated research grants from the Deutsche Forschungsgemeinschaft and the Migraine Research Foundation and honoraria from L.E.K. Consulting for telephone surveys. Dr. Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Coherex Medical, CoLucid, Böhringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Lilly, La Roche, 3M Medica, Minster, MSD, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, SanofiAventis, Weber & Weber. Financial support for research projects was provided by Allergan, Almirall, AstraZeneca, Bayer, GSK, Janssen-Cilag, Pfizer. Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF), and the European Union. He has no ownership interest and does not own stocks of any pharmaceutical company. Dr. Kurth has received investigator-initiated research funding from the US National Institutes of Health, the French National Research Agency (ANR, Agence Nationale de la Recherche), the Migraine Research Foundation, McNeil Consumer & Specialty Pharmaceuticals, and Merck; he is a consultant to i3 Drug Safety and World Health Information Science Consultants, LLC, and he has received honoraria from Genzyme, Merck, and Pfizer for educational lectures. Dr. Völzke has received research grants from the German Federal Ministry of Education and Research, the German Research Foundation, and Siemens AG to collect data for the population-based Study of Health in Pomerania. Dr. Rosskopf has received investigator-initiated research grants from the Ministry for Education, Research and Cultural Affairs of the Federal State of Mecklenburg-Vorpommern, from the German Federal Ministry of Education and Research and from Alfried Krupp von Bohlen und Halbach Foundation. F. Neumann, Dr. Kessler, and Dr. Kroemer have nothing to disclose.

M. Schürks, Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, 3rd fl, Boston, MA 02215-1204, USA.

Abstract

(Headache 2011;51:201-207)

Background.— An association between the 677C>T polymorphism (rs1801133) in the methylenetetrahydrofolate reductase gene (MTHFR) and cluster headache is plausible, but has not been investigated.

Objective.— To investigate this association among Caucasians.

Methods.— Case–control study among 147 cluster headache patients and 599 population-based age- and gender-matched controls. Cluster headache was diagnosed according to the criteria of the International Headache Society. Genotypes of the MTHFR 677C>T polymorphism were detected by restriction fragment length polymorphism analysis. We used logistic regression analysis to investigate the association between cluster headache and genotypes with additive, dominant, and recessive models. We considered a Bonferroni-corrected P value <.004 as significant.

Results.— Mean age at study entry among patients was 44.9 years (SD 11.4), of whom 76.2% were men. The genotype distribution among controls and patients was in Hardy–Weinberg equilibrium. The genotype and allele distribution did not differ between patients with any cluster headache and controls. We also did not find an association when assuming additive, dominant or recessive genetic models. When we looked at subgroups, the effect estimates suggested an increased risk for chronic cluster headache (dominant model: odds ratio = 2.82; 99.6% confidence interval = 0.72-11.07; P = .03).

Conclusions.— Data from our case–control study do not indicate an association between genotypes of the MTHFR 677C>T polymorphism and cluster headache overall. Subgroup analyses suggested that carriers of the MTHFR 677T allele may have an increased risk for chronic cluster headache. This may be regarded as hypothesis-generating and should be further investigated in independent studies.

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