RESUMO
The aim of this study was to assess the association between the TNFR1 rs2234649 polymorphism and ankylosing spondylitis susceptibility in a Russian Caucasian population. A total of 41 ankylosing spondylitis patients and 43 healthy controls, matched according to age and sex, were enrolled, and polymerase chain reaction-restriction fragment length polymorphism analysis was used to genotype the rs2234649 variant. We evaluated genotype distributions in the patient and control groups with the chi-square test, and assessed the relationship between genotypes and ankylosing spondylitis using the odds ratio. Our analysis showed that the rs2234649 polymorphism does not increase ankylosing spondylitis risk. In conclusion, the TNFR1 gene polymorphism tested does not appear to be useful for assessing predisposition to this disease or for its diagnosis or prognosis.
Assuntos
Receptores Tipo I de Fatores de Necrose Tumoral/genética , Espondilite Anquilosante/genética , Adulto , Alelos , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Polimorfismo de Nucleotídeo Único , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Federação Russa , População Branca/genéticaRESUMO
The use of clozapine and other antipsychotic drugs is known to be associated with a number of adverse metabolic side effects, including diabetes mellitus. These side effects could be, at least in part, the result of impaired islet cell function and abnormal insulin secretion, although the underlying mechanisms are unknown. The aim of this study is the identification of targets for clozapine related to the abnormal insulin secretion. We identify a specific activation of the transcriptional factor FOXA1, but not FOXA2 and FOXA3, by clozapine in HepG2 cells. Clozapine enhances FOXA1 DNA-binding and its transcriptional activity, increasing mitochondrial citrate carrier gene expression, which contains a FOXA1 site in its promoter. Haloperidol, a conventional antipsychotic drug, does not determine any increase of FOXA1 gene expression. We also demonstrate that clozapine upregulates FOXA1 and CIC gene expression in INS-1 cells only at basal glucose concentration. In addition, we find that abnormal insulin secretion in basal glucose conditions could be completely abolished by FOXA1 silencing in INS-1 cells treated with clozapine. The identification of FOXA1 as a novel target for clozapine may shed more light to understand molecular mechanism of abnormal insulin secretion during clozapine treatment.
