Searching for Predictors of Migraine Chronification: a Pilot Study of 1911A>G Polymorphism of TRPV1 Gene in Episodic Versus Chronic Migraine

Abstract

Transient receptor potential vanilloid type 1 (TRPV1) receptors activated by heat and capsaicin are expressed in trigeminal nociceptive neurons and implicated in the generation of migraine pain. Genetic studies suggested that single-nucleotide polymorphism (SNP) 1911A>G (rs8065080), leading to amino acid substitution Ile585Val, in the TRPV1 gene affects functional activity of TRPV1 receptors and is involved in different pain conditions. However, this polymorphism has not been tested in migraine patients. The objective of this pilot study was to investigate genetic factors of migraine susceptibility. We evaluated frequency distribution of AA, AG, and GG variants of SNP 1911A>G in the TRPV1 gene in patients with episodic and chronic migraine compared with healthy individuals. The study included 46 patients diagnosed with migraine (27 episodic and 19 chronic) and 50 healthy individuals as a control group. DNA from peripheral blood was used to test TRPV1 SNP using allele-specific PCR combined with gel electrophoresis. The genotype frequency distribution in episodic migraine was comparable with that in controls (AA 33%, AG 56%, GG 11% and AA 34%, AG 46%, GG 20%, respectively). On the contrary, in chronic migraine, the distribution differed significantly (p < 0.05) (AA 68%, AG 32%, GG 0%). This are first indications for a distinctive genotype frequency distribution of TRPV1 1911A>G in chronic migraine patients compared with episodic migraine patients and controls. Our data confirm a different predisposition to chronic pain in migraine and give a prerequisite for a new look at the nature of chronification of migraine, proposing that the absence of GG genotype may be considered as possible risk biomarker of episodic migraine evolution to chronic form.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank Prof. Arn M. J. M. van den Maagdenberg for the manuscript reading and providing valuable advice.

Code Availability

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Funding

The study was supported by the Russian Science Foundation (grant 15–15-20012) in the part of study design, organization, and carrying out the experiments. A.R. was supported by state assignments 20.5175.2017/6.7 and 17.9783.2017/8.9 of the Ministry of Science and Higher Education of Russian Federation in the part of carrying out theoretical work. JT was supported by the Academy of Finland (grant 316258 to J.T.) in the part of carrying out theoretical work. This study was supported by the Russian Government Program of Competitive Growth of Kazan Federal University and ITMO University.

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A.Y. performed genotyping experiments, analyzed data, and wrote the manuscript. Y.D. designed and performed the experiment and represented it in the manuscript. J.T. performed statistical analysis of data and represented it in the manuscript. A.Y., O.K., I.K., and D.N. contributed to patients’ enrolment and sample collection. A.K. and R.G. conceived the idea of the study. R.G. and A.R. discussed the results and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Aliya Yakubova.

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The study was conducted in Kazan in accordance with ethical standards presented in the Declaration of Helsinki. The Ethics Committees of the Kazan State Medical University prior the research approved the protocol of this study (permission protocol number 7 from 25.09.2018).

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Informed consent was obtained from all individual participants included in the study.

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Yakubova, A., Davidyuk, Y., Tohka, J. et al. Searching for Predictors of Migraine Chronification: a Pilot Study of 1911A>G Polymorphism of TRPV1 Gene in Episodic Versus Chronic Migraine. J Mol Neurosci 71, 618–624 (2021). https://doi.org/10.1007/s12031-020-01683-9

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Keywords

  • Migraine
  • TRPV1
  • Single-nucleotide polymorphism
  • rs8065080
  • Chronification
  • Pain sensitivity