title: HDAC3 role in medication consumption in medication overuse headache patients: a pilot study.
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.
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, SP8 Km. 0,700, 09042, Monserrato (CA), Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pisanu
authors.affiliation: Neurologic Clinic, University of Perugia, Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Caproni
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, SP8 Km. 0,700, 09042, Monserrato (CA), Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.affiliation: Headache and Cerebrovascular Diseases Center, Ospedale S. Eugenio, Rome, Italy.
authors.forename: Letizia M
authors.initials: LM
authors.lastname: Cupini
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, SP8 Km. 0,700, 09042, Monserrato (CA), Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.affiliation: Department of Pharmacy, University of Patras, School of Health Sciences, Patras, Greece. gpatrinos@upatras.gr.
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
authors.affiliation: Neurologic Clinic, University of Perugia, Perugia, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Corbelli
authors.affiliation: Neurologic Clinic, University of Perugia, Perugia, Italy.|IRCCS Fondazione "S. Lucia", Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, SP8 Km. 0,700, 09042, Monserrato (CA), Italy. delzompo@unica.it.|Institute of Neuroscience, CNR, Cagliari, Italy. delzompo@unica.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
authors.affiliation: Neurologic Clinic, University of Perugia, Perugia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sarchielli
mesh_terms: D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D051271:Headache Disorders, Secondary / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D000067490:Prescription Drug Overuse; D014635:Valproic Acid / Q000009:adverse effects; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D014635:Valproic Acid; D000099186:Histone Deacetylase 3