| 1. |
- van West, Dirk, et al.
(författare)
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Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression
- 2006
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Ingår i: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 31:3, s. 620-627
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of the hypothalamic-pituitary-adrenal axis, one of the stress-response systems, is one of the key neurobiological features of major depression (MDD). Data supporting the notion that glucocorticoid-mediated feedback inhibition is impaired in MDD come from a multitude of studies demonstrating nonsuppression of cortisol secretion following administration of the synthetic glucocorticoid dexamethasone. We examined whether genetic variations in the glucocorticoid receptor gene (Nuclear Receptor Subfamily 3, Group C, Member 1; NR3C1) could be associated with increased susceptibility for MDD using a whole gene-based association analysis of single nucleotide polymorphisms (SNPs). Four SNPs were identified in NR3C1 and genotyped in two well-diagnosed samples of patients with MDD ascertained in Belgium and northern Sweden, and matched control samples. In total, 314 MDD patients and 354 control individuals were included in the study. In the Belgian sample, we observed significant allele (p=0.02) and genotype (p=0.02) association with an SNP in the promoter region (NR3C1-1); in the Swedish sample, we observed significant allele (p=0.02) and genotype (p=0.02) association with the R23K SNP. The haplotype association studies showed modest evidence for an involvement of the 5' region of the NR3C1 gene in the genetic vulnerability for MDD. This study suggests that polymorphisms in the 5' region of the NR3C1 gene may play a role in the genetic vulnerability for MDD.
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| 2. |
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| 3. |
- Van Den Eede, Filip, et al.
(författare)
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Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in bipolar disorder
- 2007
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Ingår i: Psychiatric Genetics. - : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 17:5, s. 304-307
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Tidskriftsartikel (refereegranskat)abstract
- Corticotropin-releasing factor-binding protein regulates the availability of free corticotropin-releasing factor and is a functional candidate gene for affective disorders. The aim of this study was to examine the association between polymorphisms in CRF-BP gene and bipolar disorder in an isolated Swedish population. One hundred and eighty-two patients with bipolar I disorder and 333 controls from Northern Sweden were included in the study. Five single nucleotide polymorphisms and a deletion polymorphism in the CRF-BP gene were genotyped. The haplotype block structure of the gene was considered and the expectation maximization algorithm was adopted to estimate the haplotype frequencies. As a result, there were no significant associations of the different polymorphisms in the CRF-BP gene with bipolar disorder. In conclusion, this study in an isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder.
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| 4. |
- Van Den Eede, Filip, et al.
(författare)
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Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in recurrent major depressive disorder.
- 2007
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Ingår i: Psychiatry Research. ; 153
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Tidskriftsartikel (refereegranskat)abstract
- Corticotropin-releasingfactor-bindingprotein(CRF-BP) regulates the availability of freeCRFandisafunctional candidate gene for affective disorders. Previous research showed an association between polymorphisms in the CRF-BPgene and recurrent major depression(MDD) in a Swedish sample. The purpose of the current study was to re-evaluate the previous findings in an extended Swedish sample and in an independent Belgian sample of patients with recurrent MDD and in control samples. In total, 317 patients and 696 control individuals were included. Five single nucleotide polymorphisms (SNPs) and a deletionpolymorphismintheCRF-BP gene were genotyped and the haplotype block structure of the gene was assessed. Intheextended Swedish population, there was a trend towards an association between two SNPs and MDD. The subsequent gender analysis showed significant associations of three SNPs (CRF-BPs2T;CRF-BPs11TandCRF-BPs12C) and haplotype G_T_C_T_C with MDD in Swedish males. However, these findings did not withstand correction for multiple testing and there were nosignificant SNP or haplotype associations in the Belgian MDD sample. In conclusion, this study does not provide confirmatory evidence for a role of the CRF-BPgene in the vulnerability for MDD in general. The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample.
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| 5. |
- Van Den Eede, Filip, et al.
(författare)
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Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in recurrent major depressive disorder
- 2007
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 153:1, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- Corticotropin-releasing factor-binding protein (CRF-BP) regulates the availability of free CRF and is a functional candidate gene for affective disorders. Previous research showed an association between polymorphisms in the CRF-BP gene and recurrent major depression (MDD) in a Swedish sample. The purpose of the current study was to re-evaluate the previous findings in an extended Swedish sample and in an independent Belgian sample of patients with recurrent MDD and in control samples. In total, 317 patients and 696 control individuals were included. Five single nucleotide polymorphisms (SNPs) and a deletion polymorphism in the CRF-BP gene were genotyped and the haplotype block structure of the gene was assessed. In the extended Swedish population, there was a trend towards an association between two SNPs and MDD. The subsequent gender analysis showed significant associations of three SNPs (CRF-BPs2 T; CRF-BPs11 T and CRF-BPs12 C) and haplotype G_T_C_T_C with MDD in Swedish males. However, these findings did not withstand correction for multiple testing and there were no significant SNP or haplotype associations in the Belgian MDD sample. In conclusion, this study does not provide confirmatory evidence for a role of the CRF-BP gene in the vulnerability for MDD in general. The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample.
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| 6. |
- Massat, Isabelle, et al.
(författare)
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Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders
- 2002
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Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299 .- 1096-8628. ; 114:2, s. 177-85
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Tidskriftsartikel (refereegranskat)abstract
- Convincing evidence for a genetic component in the etiology of affective disorders (AD), including bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD), is supported by traditional and molecular genetic studies. Most arguments lead to the complex inheritance hypothesis, suggesting that the mode of inheritance is probably not Mendelian but most likely oligogenic (or polygenic) and that the contribution of genes could be moderate or weak. The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design. The following samples were analyzed for DRD2: 358 BPAD/358 control (C) and 133 UPAD/ 133 C subjects, and for DRD3: 325 BPAD/ 325 C and 136 UPAD/136 C subjects. Patients and controls were individually matched for sex, age ( plus minus five years) and geographical origin. Evidence for significant association between BPAD and DRD2 emerged, with an over-representation of genotype 5-5 (P=0.004) and allele 5 (P=0.002) in BPAD cases compared to controls. No association was found for DRD2 in UPAD, and for DRD3 neither in BPAD or UPAD. Our results suggest that the DRD2 microsatellite may be in linkage disequilibrium with a nearby genetic variant involved in the susceptibility to BPAD. Our large European sample allowed for replicating of some previous reported positive findings obtained in other study populations.
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| 7. |
- Mendlewicz, Julien, et al.
(författare)
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Expanded RED products and loci containing CAG/CTG repeats on chromosome 17 (ERDA1) and chromosome 18 (CTG18.1) in trans-generational pairs with bipolar affective disorder
- 2004
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Ingår i: American Journal of Medical Genetics. - Hoboken : John Wiley & Sons. - 0148-7299 .- 1096-8628. ; 128B:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to further test if expanded CAG repeats detected by the repeat expansion detection (RED) method in bipolar affective disorder (BPAD) are correlated with ERDA1 (17q21.3) and/or CTG18.1 (18q21.1) loci expansions, and changes of phenotype severity in successive generations (anticipation). The sample was designed to analyze ERDA1 and CTG18.1 expansions in trans-generational pairs of affected individuals (parent-offspring pairs: G1 and G2). Clinical and genetic information was available on 95 two-generations pairs. We found in our sample no one patient.
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| 8. |
- Van Den Bogaert, Ann, et al.
(författare)
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Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population
- 2006
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Ingår i: Archives of General Psychiatry. - : American Medical Association. - 0003-990X .- 1538-3636. ; 63:10, s. 1103-1110
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Tryptophan hydroxylase is the rate-limiting enzyme in the serotonin (5-HT) biosynthetic pathway responsible for the regulation of serotonin levels. Tryptophan hydroxylase 2 (TPH2) was found to be solely expressed in the brain and therefore considered an important susceptibility gene in psychiatric disorders.OBJECTIVE: To determine the role of the brain-specific TPH2 gene in unipolar (UP) disorder and bipolar (BP) disorder in a northern Swedish, isolated population.DESIGN: HapMap-based haplotype-tagging single nucleotide polymorphism (htSNP) patient-control association study.SETTING: A northern Swedish, isolated population.PARTICIPANTS: One hundred thirty-five unrelated patients with UP disorder, 182 unrelated patients with BP disorder, and 364 unrelated control individuals.RESULTS: Significant allelic association was identified in our UP disorder association sample for an htSNP located in the 5' promoter region (rs11178997; P = .001). Haplotype analysis supported this significant result by the presence of a protective factor on hapblock 2 (P(specific) = .002). In the BP disorder association sample, single-marker association identified a significant htSNP in the upstream regulatory region (rs4131348; P = .004). Moreover, haplotype analysis in the BP disorder sample showed that the same htSNPs from hapblock 2 associated with UP disorder were also significantly associated with BP disorder (P(specific) = .002).CONCLUSIONS: Haplotype-based analysis of TPH2 in patients with UP and BP disorder and controls from northern Swedish descent provides preliminary evidence for protective association in both disorders and thus supports a central role for TPH2 in the pathogenesis of affective disorders.
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| 9. |
- Van Den Bogaert, Ann, et al.
(författare)
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No allelic association or interaction of three known functional polymorphisms with bipolar disorder in a northern Swedish isolated population
- 2006
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Ingår i: Psychiatric Genetics. - : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 16:5, s. 209-212
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Tidskriftsartikel (refereegranskat)abstract
- Most genetic association studies in bipolar disorder have focussed on genes involved in major neurotransmitter systems or brain development. Functional polymorphisms in the serotonin transporter (5-HTTLPR), catechol-O-methyltransferase (Val158Met) and dopamine D3 receptor (Ser9Gly) genes have all been associated with bipolar disorder. We aimed at investigating whether these functional variants contribute to the genetic etiology of bipolar disorder in a northern Swedish isolated population. Moreover, we wanted to gain information about the synergistic contribution of these functional variants. Neither of these functional polymorphisms was associated with bipolar disorder in the northern Swedish patient-control sample nor did we find evidence of gene-gene interaction. Together, our data suggest that these functional variants are not involved in the etiology of bipolar disorder in the northern Swedish population nor did gene-gene interaction analysis support a central role of these variants in bipolar disorder.
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| 10. |
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