ASSOCIATION BETWEEN SCHIZOPHRENIA AND T102C POLYMORPHISM OF THE 5-HYDROXYTRYPTAMINE TYPE 2A-RECEPTOR GENE

Background An association between schizophrenia and the T102C polymorp hism of the gene for 5-hydroxytryptamine type 2a (5-HT2a) receptor has been reported; the proportion of allele 2 of this polymorphism is hig her than expected among schizophrenic patients. We looked for an assoc iation between schizophrenia and this variant of the 5-HT2a-receptor g ene in a large multicentre study. Methods Seven countries recruited 12 10 participants: 571 white schizophrenic patients and 639 ethnically m atched controls. All patients had a diagnosis of schizophrenia or schi zoaffective disorder. High-molecular-weight DNA was isolated from lymp hocytes. PCR amplification and restriction enzyme digestion was used t o examine sequence variation of the 5-HT2a-receptor gene. Genotypes 1/ 1, 1/2, and 2/2 were assigned. Woolf's method was used to look for an association between schizophrenia and allele 2 and the 2/2 genotype. F indings We found a significant overall association between schizophren ia and allele 2 with an odds ratio of 1.3 (95% CI 1.1-1.53, p=0.003). No evidence for heterogeneity was observed between samples. We found a highly significant excess of the 1-2/2-2 genotypes in schizophrenia ( p=0.008) with a relative risk of 1.7 (1.22-2.36) and an attributable f raction of 0.35. Interpretation Our findings suggest that the gene for 5-HT2a-receptor, or a locus in linkage disequilibrium with it, confer s susceptibility to schizophrenia. Allele 2 is common in the populatio n and it is, therefore, likely that this variant, or a nearby polymorp hism, may affect a significant proportion of schizophrenic patients.