Association study of the INPP1, 5HTT, BDNF, AP-2beta and GSK-3beta GENE variants and restrospectively scored response to lithium prophylaxis in bipolar disorder

• Published in: Neuroscience letters Vol. 403; no. 3; pp. 288 - 293
• Main Authors: Michelon, Leandro, Meira-Lima, Ivanor, Cordeiro, Quirino, Miguita, Karen, Breen, Gerome, Collier, David, Vallada, Homero
• Format: Journal Article
• Language: English
• Published: Ireland 07.08.2006
• Subjects: Antimanic Agents - therapeutic use; Bipolar Disorder - genetics; Bipolar Disorder - 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; Medicin och hälsovetenskap; Middle Aged; Phosphoric Monoester Hydrolases - genetics; Polymorphism, Genetic; Retrospective Studies; Serotonin Plasma Membrane Transport Proteins - genetics; Transcription Factor AP-2 - genetics
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2006.05.001

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.