title: Differential role of serotonergic polymorphisms in alcohol and heroin dependence.
abstract: BACKGROUND
  Twin studies suggest that genetic factors account for 40-60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence.
  
  
  METHODS
  165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods.
  
  
  RESULTS
  Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of -1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI)=1.98 (1.13-3.45) and 1.92 (1.07-3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df)=10.21 (4), p=0.037). The association of -1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups.
  
  
  CONCLUSIONS
  Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.
authors.affiliation: Department of Psychiatry, School of Medicine, University of Oviedo, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Julian Claveria 6, 33006, Oviedo, Spain. frank@uniovi.es
authors.forename: Pilar A
authors.initials: PA
authors.lastname: Saiz
authors.forename: Maria P
authors.initials: MP
authors.lastname: Garcia-Portilla
authors.forename: Gerardo
authors.initials: G
authors.lastname: Florez
authors.forename: Celso
authors.initials: C
authors.lastname: Arango
authors.forename: Paul
authors.initials: P
authors.lastname: Corcoran
authors.forename: Blanca
authors.initials: B
authors.lastname: Morales
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Bascaran
authors.forename: Cesar
authors.initials: C
authors.lastname: Alvarez
authors.forename: Gema
authors.initials: G
authors.lastname: San Narciso
authors.forename: Eduardo
authors.initials: E
authors.lastname: Carreño
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Julio
authors.initials: J
authors.lastname: Bobes