title: 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.affiliation: Department and Institute of Psychiatry (ProGene LIM-23), University of São Paulo Medical School, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Michelon
authors.forename: Ivanor
authors.initials: I
authors.lastname: Meira-Lima
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.forename: Karen
authors.initials: K
authors.lastname: Miguita
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: David
authors.initials: D
authors.lastname: Collier
authors.forename: Homero
authors.initials: H
authors.lastname: Vallada
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000235:genetics / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics
chemical_list: D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; D050656:Transcription Factor AP-2; D016651:Lithium Carbonate; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D010744:Phosphoric Monoester Hydrolases; C053087:inositol-1,4-bisphosphate 1-phosphatase