Association of AKT1 haplotype with the risk of schizophrenia in Iranian population
- 31 March 2006
- journal article
- research article
- Published by Wiley in American Journal Of Medical Genetics Part B-Neuropsychiatric Genetics
- Vol. 141B (4) , 383-386
- https://doi.org/10.1002/ajmg.b.30291
Abstract
AKT‐glycogen synthase kinase 3β (GSK3β) signaling is a target of lithium and has been implicated in the pathogenesis of mood disorders and schizophrenia. AKT1 protein level is decreased in the peripheral lymphocytes and brains of schizophrenic patients. The SNP2/3/4 TCG haplotype of AKT1 was associated with schizophrenia in patients with Northern European origin. In the present study, we genotyped five single nucleotide polymorphisms (SNP1–5) of AKT1 gene according to the original study in Iranians comprising of 321 schizophrenic patients and 383 controls, all residing in Mashhad city, Northeastern Iran. Haplotype analysis showed that the frequency of a five‐SNP haplotype (AGCAG) was significantly higher in schizophrenic patients (0.068) than that of controls (0.034) (P = 0.03 after Bonferroni correction, OR = 2.04, CI = 1.2–3.4). In stratified analysis by schizophrenia subtypes, the frequency of the same haplotype was significantly higher in disorganized subtype (n = 78, frequency of haplotype=0.081) when compared with normal controls (P = 0.04 after Bonferroni correction, OR = 2.59, CI = 1.3–5.2). Our findings did not confirm the association of AKT1 SNP2/3/4 TCG haplotype with the risk of schizophrenia as reported in the original study but showed the evidence of association with a different haplotype, AKT1 five‐SNP AGCAG haplotype, with the risk of schizophrenia in Iranian population.Keywords
This publication has 20 references indexed in Scilit:
- Association of AKT1 with schizophrenia confirmed in a Japanese populationBiological Psychiatry, 2004
- Reduced GSK-3? mRNA levels in postmortem dorsolateral prefrontal cortex of schizophrenic patientsJournal Of Neural Transmission-Parkinsons Disease and Dementia Section, 2004
- Olanzapine produces trophic effects in vitro and stimulates phosphorylation of Akt/PKB, ERK1/2, and the mitogen-activated protein kinase p38Brain Research, 2004
- Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascadeProceedings of the National Academy of Sciences, 2004
- Convergent evidence for impaired AKT1-GSK3β signaling in schizophreniaNature Genetics, 2004
- Serotonin transporter polymorphisms: no association with response to antipsychotic treatment, but associations with the schizoparanoid and residual subtypes of schizophreniaMolecular Psychiatry, 2001
- The Extent of Linkage Disequilibrium in Four Populations with Distinct Demographic HistoriesAmerican Journal of Human Genetics, 2000
- Cellular survival: a play in three AktsGenes & Development, 1999
- Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neuronsProceedings of the National Academy of Sciences, 1999
- The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinaseCell, 1995