Association of AKT1 haplotype with the risk of schizophrenia in Iranian population

Abstract

AKT-glycogen synthase kinase 3beta (GSK3beta) 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.