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Previous studies have shown a high level of heritability for most kinds of substance abuse. Certain single nucleotide polymorphisms (SNPs) or haplotypes have been shown to influence methamphetamine abuse or the related psychosis. Among the most related pathways in dependence to methamphetamine are dopaminergic system-related genes especially V-akt murine thymoma viral oncogene homolog 1 (AKT1). In the current investigation, we genotyped two intronic variants within the AKT1 gene (rs2494743 and rs2498794) in a population of Iranian methamphetamine-dependent individuals and controls. There were no significant differences in alleles, genotypes, or haplotype frequencies of rs2494743 and rs2498794 between cases and controls. Consequently, our study excludes participation of these SNPs in susceptibility to methamphetamine dependence. However, other variants within this gene might affect this trait, so future studies are needed to assess associations between other AKT1 variants and methamphetamine dependence.

Akt isoforms have critical roles in the cause and regulation of cancer cells invasive, migration, and metastatic dissemination. In the present study, the association between Akt1 polymorphisms and endometrial cancer was investigated in patients with endometrial cancer and controls. Thirty premenopaused patients diagnosed with endometrial cancer and 30 premenopaused women with no clinically documented abnormalities of the endometrium undergoing hysterectomy were included in this study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. There was no significant difference between Akt1 gene polymorphisms of patients (SNP1, SNP2 and SNP3) with endometrial cancer and controls (p > 0.05). Difference between alleles frequency of SNP1, SNP2, SNP3 of patients with endometrial cancer and controls was not significant (p > 0.05). SNPs (rs72715985), (rs2494750), and (rs74090038) of Akt1 gene are not associated with endometrial cancer in Iranian subjects.

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.