Trend for an association between schizophrenia and D3S1310, a marker in proximity to the dopamine D3 receptor gene

Abstract

There is considerable controversy regarding a putative association between schizophrenia and a biallelic BalI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3), although meta-analyses of published data suggest an association. If such an association exists, it may be detectable at markers physically close to DRD3. Accordingly, we conducted a case-control association study using D3S1310, a short tandem repeat polymorphism located approximately 700 kb telomeric to DRD3 on chromosome 3q13.3. The subjects were Swedish patients with schizophrenia (DSM III-R criteria, n = 110) and screened adult controls (n = 83). A trend for a negative association with the 141 bp allele was detected (chi2 = 7.6, d.f. = 1, P = 0.006; odds ratio 0.46, 95% confidence intervals 0.26, 0.81). However, following corrections for multiple comparisons using subgroups (n = 15) the difference was not significant. Also, due to the risk for population stratification in case-control association studies the results must be treated as tentative. If replicated the results may lend further support for the proposition of an association between schizophrenia and DRD3 or a gene in close proximity to DRD3 on chromosome 3q.

D2 but not D3 receptors are elevated after 9 or 11 months chronic haloperidol treatment: Influence of withdrawal period

“…The elevation of D 3 receptors observed in the schizophrenic group withdrawn from antipsychotic medication is unlikely to be due to release from chronic antipsychotic treatment, as we and others Fishburn et al, 1994;Florijn et al, 1997;Lévesque et al, 1995;Tarazi et al, 1997) have not found that D 3 receptor or mRNA levels are elevated with chronic antipsychotic treatment in rats. Second, gene polymorphisms in the D 3 receptor and their association with schizophrenia have been identified that may be related to subgroups of patients (Dubertret et al, 1998;Griffon et al, 1996;Jonsson et al, 1999) but many more studies have been negative in this regard (for review see Serretti et al, 1999). Our hypothesis is that the elevation of D 3 receptor may reflect a hyperdopaminergic state of the mesolimbic DA system.…”

Dopamine D2 receptor gene Ser311Cys variant and schizophrenia: association study and meta‐analysis

“…Subjects could be allocated into two groups. The first has been previously described and investigated in several reports [Jönsson et al, 1993, 1999; Jönsson, 1997; Thome et al, 1997]. Subjects were assessed for life‐time psychiatric diagnosis [DSM‐III‐R; American Psychiatric Association, 1987] and geographical origin using reviews of hospital case notes, clincal and/or structured interviews [Spitzer et al, 1986], and parish register data.…”

Candidate genes, pathways and mechanisms for bipolar (manic–depressive) and related disorders: an expanded convergent functional genomics approach

“…CDK5R1 (cyclin-dependent kinase 5, regulatory subunit 1 (p35)) ( Table 1), located at 17q11.2, activates CDK5, which, among other things, modulates dopamine signaling in neurons by phosphorylating DARPP-32. 33 GSK3b (glycogen synthase kinase 3 beta), located at 3q13.3, 34 is a downstream target of the DARPP-32 pathway, 35 and has been implicated in schizophrenia. 36 CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2)) ( [39][40][41] (Figure 5a).…”