title: Role of 2 common variants of 5HT2A gene in medication overuse headache.
abstract: OBJECTIVE
  The aim of the present study was to evaluate a possible involvement of 2 polymorphisms of the serotonin 5HT2A receptor gene (A-1438G and C516T) as risk factors for medication overuse headache (MOH) and whether the presence of these polymorphic variants might determine differences within MOH patients in monthly drug consumption.
  
  
  BACKGROUND
  Despite a growing scientific interest in the mechanisms underlying the pathophysiology of MOH, few studies have focused on the role of genetics in the development of the disease, as well as on the genetic determinants of the inter-individual variability in the number of drug doses taken per month.
  
  
  METHODS
  Our study was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism on genomic DNA extracted from peripheral blood of 227 MOH patients and 312 control subjects. Genotype-specific risks were estimated as odds ratios with associated 95% confidence intervals by unconditional logistic regression and adjusted for age and gender. A stepwise multiple linear regression analysis was employed to identify significant predictors of the number of drug doses taken per month.
  
  
  RESULTS
  No significant association was found between 5HT2A A and 1438G and C516T gene polymorphisms and MOH risk. In contrast, a higher consumption of monthly drug doses was observed among 516T 5HT2A carriers (median 50, range 13-120) compared to 516CC patients (median 30, range 12-128) (Mann-Whitney U-test, P = .018). In the stepwise multiple regression analysis, C516T 5HT2A polymorphism (P = .018) and class of overused drug (P = .047) emerged as significant, independent predictors of the monthly drug consumption in MOH patients.
  
  
  CONCLUSIONS
  Although our results do not support a major role of the A-1438G and C516T polymorphic variants of the 5HT2A gene in the susceptibility of MOH, our findings support an influence of the C516T polymorphism on the number of symptomatic drug doses taken and, possibly, on the drug-seeking behavior in these patients.
authors.affiliation: Università del Piemonte Orientale A. Avogadro, DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Novara, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Terrazzino
authors.forename: Grazia
authors.initials: G
authors.lastname: Sances
authors.forename: Francesca
authors.initials: F
authors.lastname: Balsamo
authors.forename: Michele
authors.initials: M
authors.lastname: Viana
authors.forename: Francesco
authors.initials: F
authors.lastname: Monaco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
authors.forename: Emilia
authors.initials: E
authors.lastname: Martignoni
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
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics; D058999:Drug-Seeking Behavior; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D051271:Headache Disorders, Secondary / Q000235:genetics* / Q000523:psychology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D004247:DNA