OBJECTIVE: Neurotoxic metabolites of the kynurenine pathway are thought to be implicated in the pathogenesis of schizophrenia. The enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes the initial step of the kynurenine pathway that converts tryptophan to kynurenine metabolites. IDO is induced by proinflammatory cytokines. We studied IL-1Β T-511C (rs16944), IL-1Β C3954T (rs1143634), IDO VNTR and IDO rs9657182 polymorphisms in patients with schizophrenia and controls. MATERIAL AND METHODS: Genotyping was performed in 296 patients with schizophrenia (ICD-10 F20.0) and 355 healthy controls. RESULTS: The multiple dimension reduction (MDR) analysis revealed a combination included alleles С (T-511C), Т (C3954T), V1 (VNTR) and С (rs9657182), which was associated with schizophrenia (OR 3,3 CI 95% 2,3-4,8). CONCLUSION: This is the first report of the interaction between IL-1Β and IDO genes. Further research into genes of the kynurenine pathway is needed.
Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Interleukin-1beta/genetics , Schizophrenia/genetics , Adult , Alleles , Female , Humans , Interleukin-1beta/metabolism , Kynurenine/genetics , Kynurenine/metabolism , Male , Metabolic Networks and Pathways/genetics , Minisatellite Repeats , Polymorphism, Genetic , Schizophrenia/metabolism , Tryptophan/genetics , Tryptophan/metabolism , Young Adult
Cognitive reserve (CR) postulates that individual differences in the cognitive processes or neural networks underlying task performance allow some people to cope better than others with brain damage. An aim of the study was to search for candidate genes for CR in schizophrenia. We propose that higher frequencies of low risk alleles is observed in healthy relatives of schizophrenic patients compared to patients and controls and in patients without neurocognitive deficit and with less severity of the disease compared to other patients and controls. Besides, frequencies of these alleles in patients should be similar to those in general population. Authors studied SNAP-25 and DTNBP1 genes. The polymorphism T1065G of SNAP-25 was genotyped in 278 patients with schizophrenia, 126 their relatives and 207 controls and the polymorphism P1763 of DTNBP1 was genotyped in 202 patients, 229 relatives and 262 controls. There was a trend towards the increase in the frequency of an G allele of SNAP-25 in siblings of patients. The frequency of this allele was higher in patients without neurocognitive deficit compared to patients with cognitive deficit (p=0.003) and controls (p=0.002). The allele was associated with index of cognitive functioning in patients (p=0.012) and controls (p=0.006) and with the severity of negative symptoms in patients (p=0.023). At the same time, the polymorphism T1065G was not associated with schizophrenia. Therefore, an allele G may be considered as a marker for higher CR.
Carrier Proteins/genetics , Cognition/physiology , Cognitive Reserve , DNA/genetics , Polymorphism, Genetic , Schizophrenia/genetics , Synaptosomal-Associated Protein 25/genetics , Adult , Alleles , Carrier Proteins/metabolism , Disease Progression , Dysbindin , Dystrophin-Associated Proteins , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Male , Polymerase Chain Reaction , Schizophrenia/metabolism , Schizophrenia/physiopathology , Synaptosomal-Associated Protein 25/metabolism
