Association study of the INPP1, 5HTT, BDNF, AP-2β and GSK-3β GENE variants and restrospectively scored response to lithium prophylaxis in bipolar disorder
Abstract
In the present study we investigated the influence of a series variants in genes (the serotonin transporter, glycogen synthase kinase-3beta, inositol polyphosphatase 1-phosphate, brain-derived neurotrophic factor and activator protein 2beta) related to the action of lithium carbonate, a drug used for prophylaxis in mood disorders. We used a sample of unrelated patients with bipolar disorder type I on lithium therapy for at least 2 years who met the proposed response criteria for prophylactic response. Of the 134 patients, 61 patients were considered full responders, 49 non-responders and 24 partial responders. No significant differences were observed for the genotype or allele frequencies for good, partial and poor responders for the five gene variants: for BDNF G196A (genotype: chi2 = 3.67, 4 d.f., p = 0.45; allele: chi2 = 2.31, 2 d.f., p = 0.31); for INPP1 C973A (genotype: chi2 = 1.35, 4 d.f., p = 0.85; allele: chi2 = 0.04, 2 d.f., p = 0.98); for AP-2beta [CAAA](4/5) (genotype: chi2 = 3.18; 4 d.f., p = 0.52; allele: chi2 = 0.92, 2 d.f., p = 0.063); for 5HTTLPR (genotype: chi2 = 0.67, 4 d.f., p = 0.96; allele: chi2 = 0.27, 2 d.f., p = 0.87); for GSK-3beta A-1727T (genotype: chi2 = 3.55, 4 d.f., p = 0.47; allele: chi2 = 0.48, 2 d.f., p = 0.78). These investigated variants are not predictive factors for lithium prophylactic response in our sample of bipolar disorder type I patients. However, it is still possible that a subgroup of a diverse ethnic ancestry may be predisposing to some of those variants for lithium response.
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An identified SNP in the promoter of GSK3β (−50 T to C) does not appear to be related to the degree of prophylactic lithium response in bipolar patients.
“Two studies find that an identified SNP in the promoter of this gene (−50 T to C) does not appear to be related to the degree of prophylactic lithium response in bipolar patients (Michelon et al., 2006; Szczepankiewicz et al., 2006a).”
From Circadian genes, rhythms and the biology of mood disorders (2007) · cites this paper as Michelon et al., 2006
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- Authors
- Michelon, L., Meira-Lima, I., Cordeiro, Q., Miguita, K., Breen, G., Collier, D., & Vallada, H.
- Affiliations
- Universidade de São Paulo (BR)
- King's College London (GB)
- Corresponding author
- Vallada, Homero
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 403
- Issue
- 3
- Pages
- 288-293
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1986307811
- Cited by
- 104
- References
- 42
- Citations by year
- 2026: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 11 · 2012: 6
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (00/14372-7)
- Coordenação de Aperfeiçoamento de Pessoal de NÃvel Superior (BEX 2792/05-2)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- bipolar disorder, lithium prophylaxis, genetic polymorphism, 5-HTTLPR, brain-derived neurotrophic factor, AP-2β, GSK3β, bipolar I disorder, mood stabilizers, pharmacogenetics, genotype-phenotype correlation, ethnic ancestry, antidepressant response, obsessive-compulsive disorder
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Bipolar Disorder, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Phosphoric Monoester Hydrolases, Polymorphism, Genetic, Retrospective Studies, Lithium Carbonate, Antimanic Agents, Brain-Derived Neurotrophic Factor, Glycogen Synthase Kinase 3, Serotonin Plasma Membrane Transport Proteins, Transcription Factor AP-2
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