RESUMO
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.
Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/genética , Interleucina-1beta/genética , Esquizofrenia/genética , Adulto , Alelos , Feminino , Humanos , Interleucina-1beta/metabolismo , Cinurenina/genética , Cinurenina/metabolismo , Masculino , Redes e Vias Metabólicas/genética , Repetições Minissatélites , Polimorfismo Genético , Esquizofrenia/metabolismo , Triptofano/genética , Triptofano/metabolismo , Adulto JovemRESUMO
To evaluate a role of dopamine transmission in the theory of mind (ToM) dysfunction in schizophrenia, authors studied the association of ToM with COMT and DRD2 gene polymorphisms in 209 patients with schizophrenia and 172 healthy people. All subjects performed second-order false belief (FB2) and faux pas stories. The association between the COMT Val158Met polymorphism and performance on FB2 was found. The association was sex-specific. The worse performance was associated with a Met allele in female patients and with the ValVal genotype in male ones. A correlation analysis of the COMT Val158Met polymorphism, performance on FB2 task, neurocognitive and clinical symptoms suggests that in female patients the association was modified, in part, by the higher stress sensitivity caused by the severity of clinical symptoms and its consequences for cognitive functioning.
Assuntos
Catecol O-Metiltransferase/genética , Cognição/fisiologia , DNA/genética , Polimorfismo Genético , Receptores de Dopamina D2/genética , Esquizofrenia/genética , Teoria da Mente/fisiologia , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Esquizofrenia/fisiopatologiaRESUMO
Growing evidence suggest that interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) are involved in the pathogenesis of schizophrenia. The objective of this study was to test the association of the functional promoter polymorphism 511T>C of the IL-1B gene and the VNTR polymorphism of the IL-1RN gene with clinical symptoms of schizophrenia. We studied 758 patients, 415 men and 343 women, with the ICD-10 diagnosis of schizophrenia. Symptoms of schizophrenia were measured using the Positive and Negative Symptome Scale (PANSS). The sample was stratified by gender and type of schizophrenia (chronic or episodic). We found the association between the VNTR IL-1RN polymorphism and PANSS negative symptoms (p = 0.02) in men. Male patients with the genotype 2*2 had lower scores than those with 1*2 and 1*1 genotypes. The genotype 2*2 was associated with a more severe illness course (shorter illness duration and smaller number of hospitalizations) as well. The results suggest that the VNTR polymorphism in the IL-1RN gene may be a predictor of outcome of schizophrenia in men.
