We found statistically significant DNA hypomethylation of the promoter regions of DRD3 (P = 0.032), DRD4 (P = 0.05), MB-COMT (P = 0.009), and AKT1 (P = 0.0008) associated with increased expression of the corresponding genes in patients with methamphetamine psychosis (P = 0.022, P = 0.034, P = 0.035, P = 0.038, respectively), and to a lesser degree in some of the candidate genes in non-psychotic patients versus the control subjects.
Significant associations were observed between the serotonin transporter gene (SERT) polymorphism STin2 and "psychosis"; the dopamine transporter gene (DAT) 3' variable number tandem repeats (VNTR) and "agitation"; and the dopamine receptor 4 (DRD4) VNTR and "moods" factors.
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.
Genetic polymorphisms of D2-like dopamine receptor genes, DRD2 TaqI A, DRD3 Ser-9-Gly, and DRD4 exon III variable number of tandem repeats, were compared between: (a) MAMP users as a whole and 435 normal controls, and (b) those 154 individuals with MAMP-induced psychosis and the 252 MAMP users with no psychosis.
It has been suggested that some molecular variants of the DRD4 gene (e.g., four and seven alleles) could be implicated in the pathogenesis of psychotic disorders.
This analysis in an enlarged sample suggests that DRD4*Long alleles exert a small but significant influence on the delusional symptomatology in subjects affected by major psychoses.
Our results exclude that coding variants of the DRD4 exon 1 and 3 may play a major role in conferring susceptibility to major psychoses; moreover, we could not replicate the association of DRD4 exon 1 variant with delusional disorder.
Catalano et al reported an association between delusional disorder and the number of a 12-nucleotide (bp) repeat sequence in the first exon of dopamine D4 receptor gene (DRD4), which indicated a possible role of this polymorphism in the pathogenesis of psychotic disorders.
Neither the DRD2 S311C polymorphism nor the presence of long alleles for the DRD4 exon III repeat sequence was associated with psychosis or aggression.
Genotypes of DRD4 polymorphism were analyzed for 47 schizophrenic probands who had at least one living sibling with a diagnosis of schizophrenia, 35 unaffected siblings of the schizophrenic proband, 42 sporadic schizophrenic patients, and 43 healthy controls without a family history of psychosis.