title: Association between T102C and A-1438G polymorphisms in the serotonin receptor 2A (5-HT2A) gene and schizophrenia: relevance for treatment with antipsychotic drugs.
abstract: BACKGROUND
  An involvement of serotonin receptor 2A (5-HT2A) in the aetiology of schizophrenia has been hypothesised. The 5-HT2A receptor also appears to be an important site of action of atypical antipsychotic drugs. Indeed, association between schizophrenia and the T102C silent polymorphism of the 5-HTR2A gene has been reported. Another polymorphism in the promoter region of 5-HTR2A (A-1438G) in linkage disequilibrium with the T102C polymorphism has also been reported. It has been suggested that the A-1438G polymorphism alters promoter activity and expression of 5-HT2A receptors and might be responsible for the associations with schizophrenia and the efficacy of atypical antipsychotics such as risperidone.
  
  
  METHODS
  We analysed the 5-HTR2A T102C and A-1438G polymorphisms in clinically stable schizophrenia patients (SPs) and healthy volunteers (HVs). We developed an allele-specific PCR-based restriction fragment length polymorphism (PCR-RFLP) method. In SPs, we also described differences across both diagnosis subtypes (paranoid vs. non-paranoid) and antipsychotic drug treatment (risperidone vs. other classical antipsychotic drugs).
  
  
  RESULTS
  Two groups of 114 SPs and 142 HVs were studied. The frequency of the 5-HTR2A -1438A allele was higher in SPs than in HVs (0.54 vs. 0.44; p<0.05). The frequency of the 102T allele was also higher among SPs than HVs (0.56 vs. 0.46; p<0.05). These two polymorphisms were in linkage disequilibrium. The percentage of carriers of the 1438A/A and 102T/T alleles was 26% and 15% for SPs and HVs, respectively (p<0.05; odds ratio 1.9). No differences in genotype or allele frequencies were found between paranoid and non-paranoid SPs or between SPs on risperidone and those on classical antipsychotic treatment.
  
  
  CONCLUSIONS
  The present study demonstrates a higher frequency of 5-HTR2A -1438A and 102T alleles in SPs compared to HVs.
authors.affiliation: CICAB Clinical Research Centre, Servicio Extremeño de Salud, Extremadura University Hospital, Badajoz, Spain and Faculty of Medicine, University of Extremadura, Badajoz, Spain.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Peñas-Lledó
authors.forename: Pedro
authors.initials: P
authors.lastname: Dorado
authors.forename: Macarena C
authors.initials: MC
authors.lastname: Cáceres
authors.forename: Alfredo
authors.initials: A
authors.lastname: de la Rubia
authors.forename: Adrián
authors.initials: A
authors.lastname: Llerena
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics* / Q000378:metabolism; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D018967:Risperidone