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

Human Genomics

Paola Sarchielli⁵  Maria Del Zompo¹  Paolo Calabresi³  Ilenia Corbelli⁵  George P. Patrinos⁴  Alessio Squassina⁶  Letizia M. Cupini²  Donatella Congiu⁶  Stefano Caproni⁵  Claudia Pisanu⁶ 

[1] Institute of Neuroscience, CNR, Cagliari, Italy;Headache and Cerebrovascular Diseases Center, Ospedale S. Eugenio, Rome, Italy;IRCCS Fondazione “S. Lucia”, Rome, Italy;Department of Pharmacy, University of Patras, School of Health Sciences, Patras, Greece;Neurologic Clinic, University of Perugia, Perugia, Italy;Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, SP8 Km. 0,700, Monserrato (CA), 09042, Italy

关键词: Sodium valproate;    Sequencing;    HDAC3;    Medication overuse headache;   

Others  :  1232634
DOI  :  10.1186/s40246-015-0051-1

 received in 2015-07-20, accepted in 2015-10-26,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Pisanu et al.

【 图 表 】

Fig. 1.

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