Journal of Molecular Neuroscience

, Volume 65, Issue 3, pp 367–376 | Cite as

Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms

  • Martha-Spyridoula Katsarou
  • Maria Papasavva
  • Rozana Latsi
  • Ioanna Toliza
  • Alfrent-Pantelis Gkaros
  • Stylianos Papakonstantinou
  • Stylianos Gatzonis
  • Dimos-Dimitrios Mitsikostas
  • Leda Kovatsi
  • Boris N. Isotov
  • Aristides M. Tsatsakis
  • Nikolaos DrakoulisEmail author


Cluster headache is a disorder with increased hereditary risk. Associations between cluster headache and polymorphism rs2653349 of the HCRTR2 gene have been demonstrated. The less common allele (A) seems to reduce disease susceptibility. The polymorphism rs5443 of the GNB3 gene positively influences triptan treatment response. Carriers of the mutated T allele are more likely to respond positively compared to C:C homozygotes, when treated with triptans. DNA was extracted from buccal swabs obtained from 636 non-related Southeastern European Caucasian individuals and was analyzed by real-time PCR. Gene distribution for the rs2653349 was G:G = 79.1%, G:A = 19.2%, and A:A = 1.7%. The frequency of the wild-type G allele was 88.7%. The frequencies for rs5443 were C:C = 44.0%, C:T = 42.6%, and T:T = 13.4%. The frequency of the wild-type C allele was 65.3%. The frequency distribution of rs2653349 in the Southeastern European Caucasian population differs significantly when compared with other European and East Asian populations, and the frequency distribution of rs5443 showed a statistically significant difference between Southeastern European Caucasian and African, South Asian, and East Asian populations. For rs2653349, a marginal statistically significant difference between genders was found (p = 0.080) for A:A versus G:G and G:A genotypes (OR = 2.78), indicating a higher representation of male homozygotes for the protective mutant A:A allele than female. No statistically significant difference was observed between genders for rs5443. Cluster headache pathophysiology and pharmacotherapy response may be affected by genetic factors, indicating the significant role of genotyping in the overall treatment effectiveness of cluster headaches.


GNB3 HCRTR2 Cluster headache therapy Southeastern European Caucasians Pharmacogenomics 



Cluster headache


International Headache Society


Trigeminal autonomic cephalalgias


Single-nucleotide polymorphism


Hypocretin receptor type 2




G protein beta-3 subunit


Southeastern European Caucasians


Odds ratio


Confidence intervals


Hardy–Weinberg equilibrium


Positron-emission tomography


Calcitonin-gene related peptide




Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Martha-Spyridoula Katsarou
    • 1
  • Maria Papasavva
    • 1
  • Rozana Latsi
    • 1
  • Ioanna Toliza
    • 1
  • Alfrent-Pantelis Gkaros
    • 2
  • Stylianos Papakonstantinou
    • 1
  • Stylianos Gatzonis
    • 3
  • Dimos-Dimitrios Mitsikostas
    • 4
  • Leda Kovatsi
    • 5
  • Boris N. Isotov
    • 6
  • Aristides M. Tsatsakis
    • 7
  • Nikolaos Drakoulis
    • 1
    Email author
  1. 1.Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health SciencesNational and Kapodistrian University of AthensAthensGreece
  2. 2.Department of Statistics and Insurance Science, School of Finance and StatisticsUniversity of PiraeusPiraeusGreece
  3. 3.A’ Neurosurgical Clinic, Evangelismos Hospital, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  4. 4.First Department of Neurology, Eginition Hospital, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  5. 5.Laboratory of Forensic Medicine and Toxicology, School of MedicineAristotle University of ThessalonikiThessalonikiGreece
  6. 6.Department of Analytical Toxicology, Pharmaceutical Chemistry and PharmacognosySechenov UniversityMoscowRussia
  7. 7.Laboratory of Toxicology, Medical SchoolUniversity of CreteCreteGreece

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