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Association analysis of exon III and exon I polymorphisms of the dopamine D4 receptor locus in Mexican psychotic patients.

Aguirre AJ, Apiquián R, Fresán A, Cruz-Fuentes C

Departamento de Genética Psiquiátrica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría "Ramón de la Fuente", Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, cp 14370 D.F., México.

In this study, we investigated whether polymorphisms of the dopamine D4 receptor (DRD4) gene were associated with psychotic symptomatology rather than with a unique diagnosis such as schizophrenia. A number of association studies between the DRD4 gene 48 bp-VNTR polymorphism at exon 3 and psychotic disorders have been reported, but the results have been controversial. Both 48 bp-VNTR and the 12 bp-VNTR (at exon 1) polymorphisms of this gene were analyzed in a group of 149 unrelated Mexican subjects with a diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, major depression and bipolar disorder, both with psychotic symptoms, brief psychotic disorder, delusional disorder and non-specific psychotic disorder, and in 169 individuals free of psychiatric illnesses. There were no differences in allele or genotype frequencies between groups for the 12 bp-VNTR polymorphisms. However, a significant excess of "rare" alleles (3-, 5-, 6- and 8-48 bp repeats alleles) was found in the group of psychotics. Moreover, haplotypes 3-A1, 5-A1, 6-A1 and 8-A1 were significantly more frequently associated with cases. This positive association supports a role of this molecule as a genetic risk factor in psychotic disorders.

Published 30 October 2007 in Psychiatry Res, 153(3): 209-15.
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