Clinical Chemistry and Laboratory Medicine (CCLM)
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Association between T102C and A–1438G polymorphisms in the serotonin receptor 2A (5-HT2A) gene and schizophrenia: relevance for treatment with antipsychotic drugs
1CICAB Clinical Research Centre, Servicio Extremeño de Salud, Extremadura University Hospital, Badajoz, Spain and Faculty of Medicine, University of Extremadura, Badajoz, Spain
2CICAB Clinical Research Centre, Servicio Extremeño de Salud, Extremadura University Hospital, Badajoz, Spain and Faculty of Medicine, University of Extremadura, Badajoz, Spain
First two authors contributed equally to this study
3CICAB Clinical Research Centre, Servicio Extremeño de Salud, Extremadura University Hospital, Badajoz, Spain
4Mérida Psychiatric Hospital, Mérida, Spain
5CICAB Clinical Research Centre, Servicio Extremeño de Salud, Extremadura University Hospital, Badajoz, Spain and Faculty of Medicine, University of Extremadura, Badajoz, Spain
Citation Information: Clinical Chemical Laboratory Medicine. Volume 45, Issue 7, Pages 835–838, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: 10.1515/CCLM.2007.181, July 2007
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.
Clin Chem Lab Med 2007;45:835–8.
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