HDAC3 role in medication consumption in medication overuse headache patients: A pilot study

Claudia Pisanu, Stefano Caproni, Donatella Congiu, Letizia M. Cupini, Alessio Squassina, George P. Patrinos, Ilenia Corbelli, Paolo Calabresi, Maria Del Zompo, Paola Sarchielli

Research output: Contribution to journalArticle

Abstract

Background: Medication overuse headache (MOH) is a common and debilitating disorder characterized by generation, perpetuation, and persistence of intense chronic migraine, caused by overuse of analgesics, triptans, or other acute headache compounds. It has been suggested that MOH could share some pathogenetic mechanisms with other kinds of drug addiction. In this regard, histone deacetylases 3 (HDAC3) seems to have a role in the memory processes involved in extinction of drug-seeking behavior in animal models. HDAC3 is inhibited by sodium valproate, a drug with proven efficacy in MOH. Recent evidence suggests an involvement of genetic factors in predisposition to medication overuse. Results: In this association study, we sequenced all exons, intron/exon junctions, and 3'-5'UTR regions of HDAC3 in 23 MOH patients to investigate its role in medication overuse. Associations between genotypes with continuous and dichotomous clinical characteristics were tested by multivariate analysis and Fisher's exact test, respectively. Sequencing of HDAC3 revealed six single-nucleotide polymorphisms. The G allele of rs2530223 was significantly associated with the number of acute medications/month used and with the number of days/month in which medications were used (p = 0.006 and p = 0.007, respectively), but neither with headache frequency or intensity. None of the single-nucleotide polymorphisms (SNPs) was associated with clinical characteristics or response to sodium valproate. Conclusions: HDAC3 could be implicated in excessive medication consumption in MOH patients. Our preliminary findings provide support for the need of further investigation on larger independent samples to confirm and extend the role of HDAC3 in medication overuse headache.

Original languageEnglish
Article numberA001
JournalHuman Genomics
Volume9
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

  • HDAC3
  • Medication overuse headache
  • Sequencing
  • Sodium valproate

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

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    Pisanu, C., Caproni, S., Congiu, D., Cupini, L. M., Squassina, A., Patrinos, G. P., Corbelli, I., Calabresi, P., Del Zompo, M., & Sarchielli, P. (2015). HDAC3 role in medication consumption in medication overuse headache patients: A pilot study. Human Genomics, 9(1), [A001]. https://doi.org/10.1186/s40246-015-0051-1