Support for the presence of bipolar disorder susceptibility loci on chromosome 5

Shink, Éric; Morissette, Jean; Villeneuve, A; Bordeleau, Lise; Rochette, Denis; Gagné, Bernard; Laprise, C.; Plante, M.; Barden, Nicholas

doi:10.1016/s0278-5846(02)00266-x

Cited by 17 publications

(11 citation statements)

References 20 publications

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“…a1B-AR knockout mice also showed decreased exploratory activity and fear-motivated behavior (Knauber and Muller, 2000;Stone et al, 2001). The gene for alpha 1B receptor maps to 5q33, a region investigated with suggestive results in several linkage studies of BD (Shink et al, 2002). It is interesting that a1B-AR expression is higher in bipolar patients than controls, but decreased by lithium in our study.…”

Section: Discussionsupporting

confidence: 66%

Identification of Lithium-Regulated Genes in Cultured Lymphoblasts of Lithium Responsive Subjects with Bipolar Disorder

Sun

Young

Wang

et al. 2004

Neuropsychopharmacol

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Lithium, a common drug for the treatment of bipolar disorder (BD), requires chronic administration to prevent recurrences of the illness. The necessity for long-term treatment suggests that changes in genes expression are involved in the mechanism of its action. We studied effects of lithium on gene expression in lymphoblasts from BD patients, all excellent responders to lithium prophylaxis. Gene expression was analyzed using cDNA arrays that included a total of 2400 cDNAs. We found that chronic lithium treatment at a therapeutically relevant concentration decreased the expression of seven genes in lymphoblasts from lithium responders. Five of these candidate lithiumregulated genes, including alpha1B-adrenoceptor (a1B-AR), acetylcholine receptor protein alpha chain precursor (ACHR), cAMPdependent 3 0 ,5 0 -cyclic phosphodiesterase 4D (PDE4D), substance-P receptor (SPR), and ras-related protein RAB7, were verified by Northern blotting analysis in lithium responders. None of these genes were regulated by lithium in healthy control subjects. When we compared the expression of these five genes between bipolar subjects and healthy control subjects at baseline, prior to lithium administration, we found that a1B-AR gene expression was higher in bipolar subjects than in healthy control subjects. Our findings indicate that a1B-AR may play an important role in the mechanism of action of lithium treatment.

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Section: Discussionsupporting

confidence: 66%

Identification of Lithium-Regulated Genes in Cultured Lymphoblasts of Lithium Responsive Subjects with Bipolar Disorder

Sun

Young

Wang

et al. 2004

Neuropsychopharmacol

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“…Using the transmission disequilibrium test for three polymorphisms previously described (-800T/C, -48A/G and 1403T/C), two independent groups of researchers did not fi nd a relationship between any single marker and bipolar affective disorder [13,14] . On the other hand, several linkage studies have suggested that the risk locus for bipolar affective disorder was located on the 5q chromosome, close to the DRD1 gene [15,16] . Recently, Severino et al [17] have reported a statistically signifi cant association between bipolar illness, type I, and the DRD1 -48A/G polymorphism in a Sardinian isolated population: the G/G genotype and G allele were more frequent in patients than in healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Dopamine Receptor D<sub>1</sub> Gene –48A/G Polymorphism Is Associated with Bipolar Illness but Not with Schizophrenia in a Polish Population

et al. 2006

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Dysregulation of dopaminergic neurotransmission has been implicated in the etiology of major psychoses. The dopamine D₁ receptor (DRD1) plays a role in some brain functions and mechanisms of psychotropic drugs. Therefore, the DRD1 gene makes a good candidate gene for molecular genetic studies in schizophrenia and bipolar affective disorder. In the present study, the –48A/G polymorphism of the DRD1 gene was estimated in patients with schizophrenia (n = 407) or bipolar affective disorder (n = 380), and in healthy controls (n = 399). No association was found between the polymorphism studied and schizophrenia, either in the whole group of patients or in subgroups divided by gender, age at onset or predominance of positive or negative symptoms. A statistical trend was obtained for an association between this polymorphism and bipolar affective disorder (p = 0.059 for genotypes, p = 0.073 for alleles). The G/G genotype and G allele were significantly more frequent in patients with bipolar disorder, type II (p = 0.016 for genotypes, p = 0.008 for alleles), especially in the women subgroup (p = 0.054 for genotypes, p = 0.024 for alleles). An association between the G/G genotype and bipolar affective disorder with disease onset after 18 years of age was also found (p = 0.022). These data suggest that the –48A/G polymorphism of the DRD1 gene may be involved in the etiology of bipolar disorder in a Polish population.

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“…The sequence of the dopamine D 1 receptor gene (DRD1) has been determined and mapped to chromosome 5q35.1 [Grandy et al, 1990]. To date, several linkage and association studies have reported controversial results regarding DRD1 and BP [Jensen et al, 1992;Mitchell et al, 1992;Cichon et al, 1994a;Savoye et al, 1998;Garner et al, 2001;Shink et al, 2002]. However, by using 286 trios of subjects affected by BP, Ni et al [2002] found a significant association (P-value ¼ 0.0011) between the DRD1 haplotype, À800C/À48G/1403T, and BP, suggesting that DRD1 may play a role in the etiology of this illness, even though they did not find any positive association considering each SNP singularly.…”

Section: Introductionmentioning

confidence: 99%

Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia

Zompo

Luca

Severino

et al. 2006

American J of Med Genetics Pt B

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Based on the dopaminergic hypothesis, the dopamine D(1) receptor gene (DRD1) is considered to be a good candidate gene involved in the susceptibility of bipolar disorder (BP). Genetic association between three DRD1 single nucleotide polymorphisms (SNPs) (-800T/C, -48A/G, and 1403T/C) and bipolar type I (BP I) disorder was performed in a case-control sample of Sardinian origin (170 BP I and 209 controls) and in an enlarged sample (229 families) of BP I trios from Toronto. The haplotype analyses generated significant global chi-square in both samples (P-value 0.024 in Toronto and 0.00042 in Sardinian). The main representative haplotypes in both samples were the -800T/-48A/1403C and the -800C/-48G/1403T. Considering each group individually, the -800C/-48G/1403T was transmitted more frequently from parents to BP I probands in Toronto sample (nominally P-value = 0.047) and was more frequent in cases than in control subjects in Sardinian sample although showing no significant evidence of association (nominally P-value = 0.16) When the estimated haplotype counts of both samples were combined, the global chi(2) was significant (P-value = 0.00085) and the nominal P-value for the haplotype -800C/-48G/1403T was 0.01. The fact that the same haplotype shows a similar trend for association in samples originating from different ethnic backgrounds seems to imply that the -800C/-48G/1403T haplotype may be considered as a risk factor for BP I disorder.

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Support for the presence of bipolar disorder susceptibility loci on chromosome 5

Cited by 17 publications

References 20 publications

Identification of Lithium-Regulated Genes in Cultured Lymphoblasts of Lithium Responsive Subjects with Bipolar Disorder

Identification of Lithium-Regulated Genes in Cultured Lymphoblasts of Lithium Responsive Subjects with Bipolar Disorder

Dopamine Receptor D<sub>1</sub> Gene –48A/G Polymorphism Is Associated with Bipolar Illness but Not with Schizophrenia in a Polish Population

Haplotype association study between DRD1 gene and bipolar type I affective disorder in two samples from Canada and Sardinia

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