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

Zompo, Maria Del; Luca, Vincenzo De; Severino, Giovanni; Ni, Xingqun; Mulas, S.; Congiu, Donatella; Piccardi, M.P.; Kennedy, James L.

doi:10.1002/ajmg.b.30445

Cited by 16 publications

(13 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fos is expressed following stimulation of cells and during differentiation. Lithium is well known to activate Fos in various areas of the brain [49,50]. The current result is a confirmation of the specificity of this study.…”

Section: Genes Up-regulated By Lithiumsupporting

confidence: 89%

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Fatemi

Reutiman

Folsom

2009

Biochemical Society Transactions

View full text Add to dashboard Cite

Bipolar disorder is a debilitating disorder of the brain with a lifetime prevalence of 1.0% for bipolar I, 1.1% for bipolar II disorder and 2.4-4.7% for subthreshold bipolar disorder. Medications, including lithium, have demonstrated efficacy in the treatment of bipolar disorder, but their molecular targets and mode of action are largely unknown. A few studies have begun to shed light on potential targets of lithium treatment that may be involved in lithium's therapeutic effect. We have recently conducted a microarray study of rat frontal cortex following chronic treatment (21 days) with lithium. Chronic treatment with lithium led to a significant (at least 1.5-fold) down-regulation of 151 genes and up-regulation of 57 genes. We discuss our results in the context of previous microarray studies involving lithium and gene-association studies to identify key genes associated with chronic lithium treatment. A number of genes associated with bipolar disorder, including Comt (catechol-O-methyltransferase), Vapa (vesicle-associated membrane protein-associated protein A), Dtnb (dystrobrevin beta) and Pkd1 (polycystic kidney disease 1), were significantly altered in our microarray dataset along with genes associated with synaptic transmission, apoptosis and transport among other functions.

show abstract

Section: Genes Up-regulated By Lithiumsupporting

confidence: 89%

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Fatemi

Reutiman

Folsom

2009

Biochemical Society Transactions

View full text Add to dashboard Cite

show abstract

“…Because of the suggestive evidence of dopaminergic system dysfunction and its role in the pathogenesis of neuropsychiatric disorders, DRD1 has been one of the genes investigated most extensively in these diseases. Recently, molecular genetic analysis revealed that DRD1 is associated with bipolar disorder (Del Zompo et al 2007;Severino et al 2005), ADHD (Bobb et al 2005;Misener et al 2004), ND (Comings et al 1997), and alcohol dependence (Kim et al 2007;Limosin et al 2003). The DdeI (A-48G) polymorphism in the 5Ј UTR (rs4532) has been reported to be signiWcantly associated with compulsive, addictive behaviors (Comings et al 1997;Kim et al 2007;Limosin et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Although most of them failed to show association, some have been revealed to be signiWcantly associated with bipolar disorder (Del Zompo et al 2007;Severino et al 2005), attention deWcit hyperactivity disorder (ADHD) (Bobb et al 2005;Misener et al 2004), and alcoholism (Kim et al 2007;Limosin et al 2003). As yet, little evidence for functional polymorphisms of DRD1 has been reported.…”

Section: Introductionmentioning

confidence: 99%

Significant association of DRD1 with nicotine dependence

et al. 2007

View full text Add to dashboard Cite

Epidemiologic studies have strongly implicated genetics in smoking behavior. Genes in the dopaminergic system, which mediates the reinforcing and dependence-producing properties of nicotine, are plausible candidates for roles in nicotine dependence (ND). In this study, we examined five single-nucleotide polymorphisms (SNPs) within or near the dopamine D(1) receptor gene (DRD1) for their association with ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström Test for ND (FTND). The samples were obtained from 2,037 participants representing 200 European American (EA) and 402 African American (AA) families. Although we found significant associations of SNPs rs265973, rs686, and rs4532 in the AA sample; of rs4532 in the EA sample; and of rs265975, rs686, and rs4532 in the pooled sample with various ND measures, only the association of rs686 in the AA sample and of rs686 and rs4532 in the pooled sample remained significant after correction for multiple testing. Haplotype-based association analysis revealed that haplotype C-T-A, formed by rs265973, rs265975, and rs686, was significantly associated with all three ND measures in both the AA and the pooled sample. Another haplotype, T-A-T, formed by rs265975, rs686, and rs4532, showed a significant association with FTND in the pooled sample. Furthermore, in a luciferase reporter assay, rs686, located in the 3' untranslated region, caused differential luciferase activities, indicating that rs686 is a functional polymorphism affecting expression of DRD1.

show abstract

“…Strikingly, DRD1 has recently been associated with other psychiatric disorders, including bipolar disorder, alcoholism, nicotine dependence, attention-deficit/hyperactivity disorder, and autism [Bobb et al, 2005;Del Zompo et al, 2007;Batel et al, 2008;Hettinger et al, 2008;Huang et al, 2008].…”

Section: Introductionmentioning

confidence: 99%

Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia

Hoenicka

Garrido

Ponce

et al. 2010

American J of Med Genetics Pt B

View full text Add to dashboard Cite

Dopaminergic dysfunction in the prefrontal cortex (PFC) is involved in the pathophysiology of schizophrenia. In the PFC, dopamine signalling largely depends on the D1 receptors, which are coded by the DRD1 gene, and on the regulation of dopamine levels by the enzyme catechol-O-methyltransferase (COMT). Here, we investigate the role of DRD1 and its interaction with the COMT gene in schizophrenic patients. In two gender-limited independent patient and control samples, we genotype five Tag single nucleotide polymorphisms (tagSNPs) of DRD1. The DRD1 SNP and haplotype associations, as well as interaction effects with the Val158Met COMT SNP were analyzed. In the male sample, we found the rs11746641 and rs11749676 DRD1 SNPs were associated with schizophrenia. Haplotype analyses identified the T-A-T-C-T variant related to a protective effect (P = 0.008) and the G-G-T-C-C variant that showed a tendency to be a risk factor for the disorder (P = 0.012). A logistic regression analysis revealed a significant pattern of interaction between DRD1 and COMT for both the rs11746641 (P = 0.002) and rs11749676 (P = 4.5 x 10(-5)) SNPs. DRD1-associated haplotypes were exclusively related to schizophrenia in the Val homozygous subgroup of patients (T-A-T-C-T: P = 0.003; G-G-T-C-C: P = 0.006). In females, none of the DRD1 SNPs were linked to the disorder. Our genetic data suggest that DRD1 and COMT are epistatically associated with protection against and the risk of developing schizophrenia in a gender-dependent fashion, and support the role of dopamine dysfunction at the PFC in the pathophysiology of this disorder.

show abstract

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

Cited by 16 publications

References 24 publications

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Significant association of DRD1 with nicotine dependence

Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia

Contact Info

Product

Resources

About