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Inducible nitric oxide synthase haplotype associated with migraine and aura

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Abstract

Migraine is a complex neurological disorder with a clear neurogenic inflammatory component apparently including enhanced nitric oxide (NO) formation. Excessive NO amounts possibly contributing to migraine are derived from increased expression and activity of inducible NO synthase (iNOS). We tested the hypothesis that two functional, clinically relevant iNOS genetic polymorphisms (C−1026A—rs2779249 and G2087A—rs2297518) are associated with migraine with or without aura. We studied 142 healthy women without migraine (control group) and 200 women with migraine divided into two groups: 148 with migraine without aura (MWA) and 52 with aura (MA). Genotypes were determined by real-time polymerase chain reaction using the Taqman® allele discrimination assays. The PHASE 2.1 software was used to estimate the haplotypes. The A allele for the G2087A polymorphism was more commonly found in the MA group than in the MWA group (28 vs. 18%; P < 0.05). No other significant differences in the alleles or genotypes distributions were found (P > 0.05). The haplotype combining both A alleles for the two polymorphisms was more commonly found in the MA group than in the control group or in the MWA group (19 vs. 10 or 8%; P = 0.0245 or 0.0027, respectively). Our findings indicate that the G2087A and the C−1026A polymorphism in the iNOS gene affect the susceptibility to migraine with aura when their effects are combined within haplotypes, whereas the G2087A affects the susceptibility to aura in migraine patients. These finding may have therapeutic implications when examining the effects of selective iNOS inhibitors.

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Acknowledgments

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior.

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Authors and Affiliations

  1. Department of Pharmacology, State University of Campinas, Campinas, SP, Brazil

    Thiago de O. S. Mansur & Flavia M. Gonçalves

  2. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, SP, 14049-900, Brazil

    Alisson Martins-Oliveira, Riccardo Lacchini & Jose E. Tanus-Santos

  3. Division of Neurology, Department of Neuroscience, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil

    Jose G. Speciali & Fabiola Dach

Authors
  1. Thiago de O. S. Mansur
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  2. Flavia M. Gonçalves
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  3. Alisson Martins-Oliveira
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  4. Jose G. Speciali
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  5. Fabiola Dach
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  6. Riccardo Lacchini
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  7. Jose E. Tanus-Santos
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Correspondence to Jose E. Tanus-Santos.

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de O. S. Mansur, T., Gonçalves, F.M., Martins-Oliveira, A. et al. Inducible nitric oxide synthase haplotype associated with migraine and aura. Mol Cell Biochem 364, 303–308 (2012). https://doi.org/10.1007/s11010-012-1231-0

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  • DOI: https://doi.org/10.1007/s11010-012-1231-0

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