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Interaction among nitric oxide (NO)-related genes in migraine susceptibility

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Abstract

The pathogenic mechanisms involved in migraine are complex and not completely clarified. Because there is evidence for the involvement of nitric oxide (NO) in migraine pathophysiology, candidate gene approaches focusing on genes affecting the endothelial function have been studied including the genes encoding endothelial NO synthase (eNOS), inducible NO synthase (iNOS), and vascular endothelial growth factor (VEGF). However, investigations on gene–gene interactions are warranted to better elucidate the genetic basis of migraine. This study aimed at characterizing interactions among nine clinically relevant polymorphisms in eNOS (T−786C/rs2070744, the 27 bp VNTR in intron 4, the Glu298Asp/rs1799983, and two additional tagSNPs rs3918226 and rs743506), iNOS (C−1026A/rs2779249 and G2087A/rs2297518), and VEGF (C−2578A/rs699947 and G−634C/rs2010963) in migraine patients and control group. Genotypes were determined by real-time polymerase chain reaction using the Taqman® allele discrimination assays or PCR and fragment separation by electrophoresis in 99 healthy women without migraine (control group) and in 150 women with migraine divided into two groups: 107 with migraine without aura and 43 with aura. The multifactor dimensionality reduction method was used to detect and characterize gene–gene interactions. We found a significant interaction between eNOS rs743506 and iNOS 2087G/A polymorphisms in migraine patients compared to control group (P < 0.05), suggesting that this combination affect the susceptibility to migraine. Further studies are needed to determine the molecular mechanisms explaining this interaction.

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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

    Flavia M. Gonçalves

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

    Marcelo R. Luizon, Alisson Martins-Oliveira & Jose E. Tanus-Santos

  3. Division of Neurology, Department of Neuroscience, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil

    Jose G. Speciali & Fabiola Dach

Authors
  1. Flavia M. Gonçalves
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  2. Marcelo R. Luizon
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  3. Jose G. Speciali
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  4. Alisson Martins-Oliveira
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  5. Fabiola Dach
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  6. Jose E. Tanus-Santos
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Corresponding author

Correspondence to Jose E. Tanus-Santos.

Additional information

Flavia M. Gonçalves and Marcelo R. Luizon contributed equally to this work.

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Gonçalves, F.M., Luizon, M.R., Speciali, J.G. et al. Interaction among nitric oxide (NO)-related genes in migraine susceptibility. Mol Cell Biochem 370, 183–189 (2012). https://doi.org/10.1007/s11010-012-1409-5

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  • DOI: https://doi.org/10.1007/s11010-012-1409-5

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