Supportive evidence for the association between the T102C 5-HTR2A gene polymorphism and schizophrenia: a large-scale case-control and family-based study

Abstract

Serotonin type 2A receptors (5-HTR2A) have long been implicated in schizophrenia pathology. A decreased number of these receptors were found in postmortem brain studies of schizophrenic patients as well as in experiments using neuroimaging techniques. Molecular genetic studies revealed that the T102C polymorphism of the 5-HTR2A gene is associated with schizophrenia, with the CC genotype frequency being higher in patients compared to healthy controls. However the association was not confirmed in all studies. We carried out a replication study, which aimed at searching for association between this polymorphism and schizophrenia in a large samples of patients (n=919), their psychiatrically well first-degree relatives (n=330) and screened controls (n=500). The C allele and the CT+CC genotype frequencies were significantly higher in patients than in controls (chi2=5.1; df=1; p=0.02; OR 1.2, 95% CI 1.0-1.4) and chi2=5.4; df=1; p=0.02; OR 1.4, 95% CI 1.1-1.8 respectively). In a family-based study, the transmission disequilibrium test (TDT) and the family-based association test (FBAT) did not show a preferential transmission of any allele. In conclusion, our replication study provides further evidence for association between the 5-HTR2A receptor T102C polymorphism and schizophrenia.