title: Combined effect of common gene variants on response to drug withdrawal therapy in medication overuse headache.
abstract: OBJECTIVE
  No information is currently available on genetic determinants of short-term response to drug withdrawal in medication overuse headache (MOH). In the present study, we aimed to evaluate the role of 14 polymorphisms in 8 candidate genes potentially relevant for drug addiction (OPRM1, DRD2, DBH, COMT, BDNF, SLC6A4, 5HT2A, and SLC1A2) as predictors for detoxification outcome of MOH patients at 2 months of follow-up.
  
  
  METHODS
  Genotyping was conducted by PCR, PCR-RFLP analysis, or real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. The association between gene variants and risk of unsuccessful detoxification was evaluated by univariate and multivariate logistic regression analyses.
  
  
  RESULTS
  One hundred and eight MOH patients with effective drug withdrawal therapy and 65 MOH patients with unsuccessful detoxification were available for the analysis. In the multivariable logistic regression analysis, triptan overuse (odds ratio (OR) 0.271, 95% confidence interval (CI) 0.083-0.890, P = 0.031) and TT genotype carriage of DRD2 NcoI (OR 0.115, 95% CI 0.014-0.982, P = 0.048) emerged as independent predictors for unsuccessful detoxification. In addition, carriers of at least four of the six top-ranked gene variants (P < 0.10) were found at higher odds for unsuccessful detoxification than patients with ≤3 high-risk genotypes (OR 3.40, 95% CI 1.65-7.01, P = 0.001).
  
  
  CONCLUSIONS
  This exploratory study suggests that DRD2 NcoI may be a genetic determinant of detoxification outcome in MOH patients. Our findings also show that an approach based on the combination of multiple genetic markers could be clinically useful for identification of MOH patients at higher risk for unsuccessful detoxification.
authors.affiliation: Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, 28100, Novara, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cargnin
authors.forename: Michele
authors.initials: M
authors.lastname: Viana
authors.forename: Grazia
authors.initials: G
authors.lastname: Sances
authors.forename: Marika
authors.initials: M
authors.lastname: Bianchi
authors.forename: Natascia
authors.initials: N
authors.lastname: Ghiotto
authors.forename: Cristina
authors.initials: C
authors.lastname: Tassorelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Canonico
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: Salvatore
authors.initials: S
authors.lastname: Terrazzino
mesh_terms: D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D051271:Headache Disorders, Secondary / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D060888:Real-Time Polymerase Chain Reaction; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012189:Retrospective Studies; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
chemical_list: D000700:Analgesics; C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2
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