RESUMEN
An analysis of the association of paranoid schizophrenia seeking with polymorphic variants of GRIN2B gene was performed in order to identify genetic risk factors of disease development and genetic markers of the response to therapy by neuroleptics in Russian and Tatar patients from Bashkortostan Republic (BB). In the course of the analysis, we revealed the following: 1) genetic markers of increased risk of developing paranoid schizophrenia in various ethnic groups, including, in Tatars, the GRIN2B* T/*Tgenotype (p = 0.003; OR = 2.33) and GRIN2B*T allele (p = 0.001; OR = 2.36), rs1805247; in Russians, the GRIN2B*T/*T genotype (p = 0.038; OR = 2.12) and GRIN2B* T allele (p = 0.028; OR = 2.03), rs1805247, genotype GRIN2B*A/*A (p = 0.042; OR = 2.12), rs1805476; 2) genetic markers of the reduced risk of developing paranoid schizophrenia; 3) genetic markers of therapy response and the risk of side effects development during neuroleptics (haloperidol) treatment in Bashkortostan. The significant interethnic diversity of genetic factors related to the risk of this disease development was noted.
Asunto(s)
Antipsicóticos/uso terapéutico , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia Paranoide/tratamiento farmacológico , Esquizofrenia Paranoide/genética , Adulto , Baskiria/etnología , Estudios de Casos y Controles , Etnicidad/genética , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Población Blanca/genéticaRESUMEN
Schizophrenia is a common psychiatric disorder affecting about 1% of the general population. Several lines of evidence indicate that Regulator of G Protein Signaling 2 (RGS2) contributes to schizophrenia vulnerability because it modulates signal transduction of neurotransmitter receptors that play a role in the pathogenesis of schizophrenia. A number of studies have shown an association of polymor- phic loci RGS2 gene with the occurrence of extrapyramidal symptoms induced by neuroleptics. DNA samples of 258 patients with paranoid schizophrenia and of 263 healthy controls of Russian and Tatar ethnic group living in the Republic of Bashkortostan were involved into the present study. In the result of the present study low risk genetic markers; high risk genetic markers of paranoid schizophrenia RGS2*G/*G (rs2746071) in Russians (p = 0.001; OR = 4.08) and in Tatars (p = 0.000; OR = 4.88); allele.RGS2*G in Russians (p = 0.00003; OR = 2.37) and Tatars (p = 0.000; OR = 2.51), high risk genetic markers of parkinsonism induced by haloperidol: RGS2*T/*T(rs2746073), RGS2*C/*C (rs4606), RGS2*A/*A (rs2746071) in Rus- sians, genetic markers of treatment efficacy in Tatars were obtained in individuals from the Republic of Bash- kortostan; considerable inter-ethnic diversity of genetic risk factors for this disease was revealed The results of this study are consistent previous results and support the hypothesis that polymorphic loci RGS2 gene associated with risk of extrapyramidal symptoms induced by typicalneuroleptics-haloperidol, and are involved in schizophrenia pathway.
Asunto(s)
Antipsicóticos/administración & dosificación , Enfermedades de los Ganglios Basales/genética , Haloperidol/administración & dosificación , Proteínas RGS/genética , Esquizofrenia/genética , Adulto , Enfermedades de los Ganglios Basales/patología , Etnicidad/genética , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Marcadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/patologíaRESUMEN
We have developed a biochip for the analysis of candidate genes for schizophrenia. Using this biochip, allele and genotype frequencies for the polymorphisms of HTR2A, BDNF and SLC6A4 genes in 198 patients with schizophrenia and 192 healthy individuals have been obtained. The allele T of the HTR2A polymorphism rs6314 was identified as protective against the development of paranoid schizophrenia (p=0,014). An analysis of gene-gene interactions using the Multifactor-Dimensionality Reduction (MDR) algorithm has shown a statistically significant association of combined genotypes rs6311 G/-, rs6313 C/-, rs6314 C/C, rs7997012 G/- with the disease (p=0.019). Also it has been shown that the G/G genotype of the polymorphism rs6311 (p=0.013) and the C/C genotype of the polymorphism rs6313 (p=0.008) in the HTR2A gene are associated with the suicide attempt in schizophrenic patients. Correspondingly, an A allele, Ð/- genotypes of the polymorphism rs6311 G>A and a T allele, T/- genotypes of the polymorphism rs6313 C>T were found to be less frequent in schizophrenic patients with a history of suicide attempt than in schizophrenic patients without a history of suicide attempt, thus suggesting their protective role in the development of suicidal behavior. The results confirm the hypothesis that the HTR2A plays an important role in the etiology of schizophrenia and suicidal behavior.
