The 3' region of the DRD2 gene is involved in genetic susceptibility to schizophrenia.

The gene coding for the D2 dopamine receptor (DRD2) is considered as one of the most relevant candidate genes in schizophrenia. Previous genetic studies focusing on this gene yielded conflicting results, for example because of differences in methodology (linkage versus association studies) and variability in the loci analyzed (the DRD2 gene having many polymorphic sites). We used a progressive strategy with two different approaches (case-control and transmission disequilibrium test) and investigated six genetic polymorphisms spanning the DRD2 gene in 103 patients with DSM-IV criteria of schizophrenia, their 206 parents and 83 matched healthy control subjects. We found a significant excess of the A2 allele in subject with schizophrenia compared to unaffected controls. An excess of transmission of the A2 allele (and haplotypes containing this marker) from the parents to the affected children was also observed. Interestingly, the TaqI A1/A2 polymorphism, located 9.5 kb downstream from the DRD2 gene, maps in a novel gene, untitled "X-kinase", and leads to a 713Glu-->Lys substitution in exon 8. As the analysis of the other markers within the DRD2 gene does not improve the strength of the association, our data are in favor of a specific role of the 3' chromosomic region of the DRD2 gene in the vulnerability to schizophrenia.