Association study of the INPP1, 5HTT, BDNF, AP-2beta and GSK-3beta 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.

• Authors: Leandro Michelon, Ivanor Meira-Lima, Quirino Cordeiro, Karen Miguita, Gerome Breen, David Collier, Homero Vallada
• Journal: Neuroscience letters (Neurosci Lett) Vol. 403 Issue 3 Pg. 288-93 (Aug 07 2006) ISSN: 0304-3940 [Print] Ireland
• PMID: 16787706 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimanic Agents
• Brain-Derived Neurotrophic Factor
• Serotonin Plasma Membrane Transport Proteins
• Transcription Factor AP-2
• Lithium Carbonate
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3
• Phosphoric Monoester Hydrolases
• inositol-1,4-bisphosphate 1-phosphatase

Topics

• Antimanic Agents (therapeutic use)
• Bipolar Disorder (genetics, prevention & control)
• Brain-Derived Neurotrophic Factor (genetics)
• Female
• Gene Frequency
• Genotype
• Glycogen Synthase Kinase 3 (genetics)
• Glycogen Synthase Kinase 3 beta
• Humans
• Lithium Carbonate (therapeutic use)
• Male
• Middle Aged
• Phosphoric Monoester Hydrolases (genetics)
• Polymorphism, Genetic
• Retrospective Studies
• Serotonin Plasma Membrane Transport Proteins (genetics)
• Transcription Factor AP-2 (genetics)