Given that the switch from G to T in SNP rs3791878 might cause the loss of ARNT and XBP1 transcriptional factor binding sites using a bioinformatics approach, our positive findings of this SNP support the hypothesis that the abruption of GAD1 gene is important to the risk of schizophrenia.
These coincident results implicate GAD1 in the etiology of schizophrenia and suggest that the mechanism involves altered cortical GABA inhibitory activity, perhaps modulated by dopaminergic function.
These findings suggest that the GABRB2 and GAD1 genes alone and the combined effects of the polymorphisms in the four GABAergic system genes may confer susceptibility to the development of schizophrenia in the Chinese population.
These observations, when taken together with the positive results reported recently in two independent adult-onset schizophrenia pedigree samples, suggest that the gene encoding GAD67 may be a common risk factor for schizophrenia.
Although the levels of GAD65 and GAD67 messages were increased in schizophrenia subjects, the proportion of the two GAD isoforms remained constant in controls and schizophrenics.