title: Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of patients with medication overuse headache after withdrawal therapy.
abstract: OBJECTIVE
  It is currently unknown if common genetic variants influence the prognosis of patients with medication overuse headache (MOH). Here the role of two common single nucleotide polymorphisms in the COMT gene (rs4680 and rs6269), as well as the STin2 variable number tandem repeat (VNTR) polymorphism in the SLC6A4 gene, were evaluated as predictors for long-term outcomes of MOH patients after withdrawal therapy.
  
  
  METHODS
  Genotyping was conducted by polymerase chain reaction (PCR), PCR restriction fragment length polymorphism analysis or real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. Gene variants association was evaluated by logistic regression analysis adjusted for clinical confounding factors, and the threshold of statistical significance for multiple testing was set at P < 0.012.
  
  
  RESULTS
  Sixty-five MOH patients with unsuccessful detoxification and 83 MOH patients with effective drug withdrawal therapy were available for the analysis. rs4680G allele carriers or the COMT rs6269G-rs4680G haplotype were found to be associated with a lower risk of relapse within the first year after successful detoxification therapy, in comparison with homozygous rs4680A allele carriers [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.05-0.61, P = 0.007] or with the COMT rs6269A-rs4680A haplotype (OR 0.19, 95% CI 0.06-0.54, P = 0.003), respectively. In addition, carriers of the STin2 VNTR short allele were found at higher odds for the composite poor outcome including unsuccessful withdrawal therapy and relapse within 12 months of follow-up after successful detoxification (OR 2.81, 95%CI 1.26-6.25, P = 0.009).
  
  
  CONCLUSIONS
  Our results indicate that genotyping for COMT rs4680 and SLC6A4 STin2 VNTR could be useful for the identification of MOH patients at higher risk of poor prognosis after drug withdrawal.
authors.affiliation: Dipartimento di Scienze del Farmaco and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Università del Piemonte Orientale 'A. Avogadro', Novara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cargnin
authors.forename: M
authors.initials: M
authors.lastname: Viana
authors.forename: N
authors.initials: N
authors.lastname: Ghiotto
authors.forename: M
authors.initials: M
authors.lastname: Bianchi
authors.forename: G
authors.initials: G
authors.lastname: Sances
authors.forename: C
authors.initials: C
authors.lastname: Tassorelli
authors.forename: G
authors.initials: G
authors.lastname: Nappi
authors.forename: P L
authors.initials: PL
authors.lastname: Canonico
authors.forename: A A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: S
authors.initials: S
authors.lastname: Terrazzino
mesh_terms: D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D051271:Headache Disorders, Secondary / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011379:Prognosis; D012008:Recurrence; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: COMT; SLC6A4; detoxification; medication overuse headache; polymorphisms; relapse