Polymorphisms in the Renin-Angiotensin System and Migraine in Women

Authors

  • Markus Schürks MD, MSc,

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    • *

      These authors contributed equally to the work.

  • Robert Y. L. Zee MD, PhD,

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    • *

      These authors contributed equally to the work.

  • Julie E. Buring ScD,

    1. From the Division of Preventive Medicine, Department of Medicine; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA (M. Schürks, R.Y.L. Zee, J.E. Buring, and T. Kurth); Division of Aging, Department of Medicine; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA (J.E. Buring and T. Kurth); Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA (J.E. Buring and T. Kurth); Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA, USA (J.E. Buring).
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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, MA, USA (M. Schürks, R.Y.L. Zee, J.E. Buring, and T. Kurth); Division of Aging, Department of Medicine; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA (J.E. Buring and T. Kurth); Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA (J.E. Buring and T. Kurth); Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA, USA (J.E. Buring).
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  • Funding and support: The Women's Health Study is supported by grants from the National Heart, Lung, and Blood Institute (HL-43851), and the National Cancer Institute (CA-47988). The research for this work was supported by grants from the Donald W. Reynolds Foundation, the Leducq Foundation, and the Doris Duke Charitable Foundation. The authors also thank F. Hoffmann La-Roche and Roche Molecular Systems, Inc. for supporting the genotype-determination financially and with in-kind contribution of reagents and consumables. Dr. Schürks was supported by a grant from the Deutsche Forschungsgemeinschaft (SCHU 1553/2-1). The funding agencies played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

  • Conflict of Interest: Dr. Schürks has received within the last 5 years investigator-initiated research funds from the Deutsche Forschungsgemeinschaft and an unrestricted research grant from Merck, Sharp and Dohme. Dr. Zee has received within the last 5 years research support from the National Heart, Lung, and Blood Institute, the Doris Duke Charitable Foundation, the Leducq Foundation, the Donald W. Reynolds Foundation, and Roche. Dr. Kurth has received within the last 5 years investigator-initiated research funding as Principal or Co-Investigator from the National Institutes of Health, Bayer AG, Merck, McNeil Consumer & Specialty Pharmaceuticals, and Wyeth Consumer Healthcare; he is a consultant to i3 Drug Safety, and received honoraria from Organon for contributing to an expert panel, and from Genzyme for educational lectures. Dr. Buring has received within the last 5 years investigator-initiated research funding and support as Principal Investigator from the National Institutes of Health and Dow Corning Corporation; research support for pills and/or packaging from Bayer Heath Care and the Natural Source Vitamin E Association; honoraria from Bayer for speaking engagements; and serves on an external scientific advisory committee for a study by Procter & Gamble.

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

Abstract

Background.— Recent findings suggest an association between the renin-angiotensin system and migraine. However, genetic studies are scarce and controversial.

Objective.— To investigate the association between the AGTR1 1166A > C and AGT Met235Thr polymorphisms with migraine and migraine aura status.

Methods.— We performed an association study among 25,000 Caucasian US women, participating in the Women's Health Study, with information on the AGTR1 1166A > C and AGT Met235Thr polymorphisms. Migraine and migraine aura status were self-reported. We distinguished between any history of migraine, active migraine with aura, active migraine without aura, and prior migraine (history of migraine, but not in the year prior to baseline). We used logistic regression to investigate the genotype–migraine association.

Results.— At baseline, 4577 (18.3%) women reported any history of migraine; 39.5% of the 3226 women with active migraine indicated aura. The polymorphisms were not associated with migraine or migraine-specific subgroups. We also did not find a significant interaction between the polymorphisms.

Conclusions.— Data from this large cohort of Caucasian women do not suggest an association of polymorphisms in the renin-angiotensin system with migraine or aura status. Future studies should focus on haplotype analyses and additional gene–gene as well as gene–environment interactions.

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