RESUMEN
Rheumatoid arthritis (RA) is a major cause of adult chronic inflammatory arthritis and an autoimmune disease of unknown etiology in which the inflammatory pathology involves T cell activation. Genetic mutations in the Mediterranean fever (MEFV) gene, encoding pyrin, influence the severity of RA, but the underlying mechanisms are not completely understood. In this study, we investigated whether the full-length MEFV gene (MEFV-fl) and the exon 2-deleted splice isoform (MEFV-d2) expression are associated with or responsible for the clinical conditions of RA. This study include 47 patients with RA and 47 age- and gender-matched healthy controls. Quantitative real-time polymerase chain reaction analysis was performed to examine transcriptional changes in MEFV gene expression from peripheral blood samples. Reverse transcription-polymerase chain reaction of peripheral blood cells revealed the downregulation of MEFV-fl mRNA in non-treated patients compared with healthy controls and treated patients. MEFV-d2 expression was not different between groups. This is the first study to investigate the expression of MEFV transcript in RA. Deregulation of the MEFV gene is likely to result in uncontrolled inflammation as observed in RA. Therefore, downregulation of MEFV-fl may be involved in the pathogenesis of early-stage RA and treatment and may ameliorate MEFV-fl expression.
Asunto(s)
Artritis Reumatoide/genética , Proteínas del Citoesqueleto/genética , Regulación de la Expresión Génica/genética , Predisposición Genética a la Enfermedad , Adulto , Anciano , Artritis Reumatoide/patología , Proteínas del Citoesqueleto/biosíntesis , Exones , Femenino , Estudios de Asociación Genética , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , Pirina , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Factores de RiesgoRESUMEN
Increased oxidative stress can help promote carcinogenesis, including development of renal cell carcinoma. The enzyme protects low-density lipoproteins from oxidation and can be a factor in this process. PON1 Q192R and L55M paraoxonase gene polymorphisms were assessed in 60 renal cell carcinoma patients and 60 healthy controls. Genotypes were examined by PCR; the restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the control group. No significant differences were found in the L55M polymorphism. Additionally, there were no significant differences in L and M allele frequencies. We conclude that the R allele may protect against renal cell carcinoma.
Asunto(s)
Arildialquilfosfatasa/genética , Carcinoma de Células Renales/genética , Polimorfismo Genético/genética , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Male infertility is a common barrier that prevents successful conception. There have been reports of azoospermia in men with familial Mediterranean fever, some of whom had not been treated with colchicine. Variation in this disorder could be a risk factor for amyloidosis associated with azoospermia. We determined the frequency of 6 of the most common Mediterranean fever gene mutations, M680I, M694V, M694I, V726A, P369S, and A744S, in 74 infertile men, 155 men diagnosed with familial Mediterranean fever and 55 healthy fertile men in eastern Turkey. All three groups were screened for the 6 mutations using an amplification refractory mutation system and restriction fragment length polymorphism methods. Allelic frequencies were 2.7% for M694V and 1.35% for V726A in the infertile patient group and 1.8% for M694V and 1.8% for V726A in healthy subjects. Other mutations were not detected in patients or controls. The mutation frequency was not found to be significantly higher in infertile patients when compared with healthy fertile male controls. To our knowledge, this is the first study to determine the frequency of Mediterranean fever gene mutations in infertile male and the infertility rate of male patients with familial Mediterranean fever.