RESUMO
Abstract Background: Although not fully understood, oxidative stress has been implicated in the pathogenesis of different autoimmune diseases such as systemic sclerosis. Accumulating evidence indicates that oxidative stress can induce mitochondrial DNA (mtDNA) damage and variations in mtDNA copy number (mtDNAcn). Objective: The aim of this study was to explore mtDNAcn and oxidative DNA damage byproducts in peripheral blood of patients with systemic sclerosis and healthy controls. Methods: Forty six patients with systemic sclerosis and forty nine healthy subjects were studied. Quantitative real-time PCR used to measure the relative mtDNAcn and the oxidative damage (oxidized purines) of each sample. Results: The mean mtDNAcn was lower in patients with systemic sclerosis than in healthy controls whereas the degree of mtDNA damage was significantly higher in cases as compared to controls. Moreover, there was a negative correlation between mtDNAcn and oxidative DNA damage. Study limitations: The lack of simultaneous analysis and quantification of DNA oxidative damage markers in serum or urine of patients with systemic sclerosis and healthy controls. Conclusion: These data suggest that alteration in mtDNAcn and increased oxidative DNA damage may be involved in the pathogenesis of systemic sclerosis.
Assuntos
Humanos , Masculino , Feminino , Adulto , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/sangue , Dano ao DNA , DNA Mitocondrial/genética , DNA Mitocondrial/sangue , Estresse Oxidativo/genética , Variações do Número de Cópias de DNA , Valores de Referência , Estudos de Casos e Controles , Espécies Reativas de Oxigênio/sangue , Estatísticas não Paramétricas , Eletroforese em Gel de Ágar , Reação em Cadeia da Polimerase em Tempo Real , Pessoa de Meia-IdadeRESUMO
ABSTRACT Objectives: To assess the association between hyperuricemia and different neuropsychiatric manifestations and stroke risk factors in systematic lupus erythematosus (SLE) patients. Methods: This study was conducted on 204 SLE patients who were admitted to a tertiary referral center. A standardized questionnaire was completed for all the participants and the medical records were reviewed regarding the occurrence of arterial or venous thrombotic events, stroke, seizure, depression, headache, psychosis, and peripheral neuropathy. In addition blood samples were drawn to obtain serum uric acid, triglyceride (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol levels. Results: Hyperuricemia (serum uric acid ≥6 mg/dl for women and ≥7 mg/dl for men) was detected in 16.1% of SLE patients and was significantly associated with the occurrence of stroke (OR, 2.38; 95%CI, 1.2-7.24), and peripheral neuropathy (OR, 3.49; 95% CI, 1.52-12.23), independent of hypertension and hyperlipidemia. Hyperuricemia was also significantly associated with hypertension (OR, 7.76; 95% CI, 2.72-15.76), hyperlipidemia (OR, 5.05; 95% CI, 1.59-11.32), and history of arterial thrombosis (OR, 4.95; 95% CI, 1.98-15.34), independent of age and body mass index. Conclusions: Hyperuricemia in SLE patients is independently associated with the occurrence of stroke and peripheral neuropathy. It is also independently associated with hypertension, hyperlipidemia, and history of arterial thrombosis, which are the major stroke and myocardial infarction risk factors in SLE patients.
RESUMO Objetivos: Avaliar a associação entre a hiperuricemia e diferentes manifestações neuropsiquiátricas e os fatores de risco para AVE em pacientes com lúpus eritematoso sistêmico (LES). Métodos: Este estudo foi feito em 204 pacientes com LES que foram internados em um centro de referência de atenção terciária. Todos os participantes preencheram um questionário padronizado e os prontuários médicos foram analisados quanto à ocorrência de eventos trombóticos arteriais ou venosos, acidente vascular encefálico, convulsão, depressão, cefaleia, psicose e neuropatia periférica. Além disso, foram coletadas amostras de sangue para se mensurarem os níveis de ácido úrico, triglicerídeos (TG), lipoproteínas de alta densidade (HDL), lipoproteínas de baixa densidade (LDL) e colesterol total do sangue. Resultados: A hiperuricemia (ácido úrico sérico ≥ 6 mg/dL para mulheres e ≥ 7 mg/dL para homens) foi detectada em 16,1% dos pacientes com LES e esteve significativamente associada à ocorrência de AVE (OR, 2,38; IC 95%, 1,2-7,24) e neuropatia periférica (OR, 3,49; IC 95%, 1,52-12,23), independentemente da hipertensão arterial e da hiperlipidemia. A hiperuricemia também esteve significativamente associada à hipertensão arterial (OR, 7,76; IC 95%, 2,72-15,76), hiperlipidemia (OR, 5,05; IC 95%, 1,59-11,32) e história de trombose arterial (OR, 4,95; 95% CI, 1,98-15,34), independentemente da idade e do índice de massa corporal. Conclusões: A hiperuricemia em pacientes com LES está independentemente associada à ocorrência de acidente vascular encefálico e neuropatia periférica. Também está independentemente associada à hipertensão, hiperlipidemia e história de trombose arterial, que são os principais fatores de risco para acidente vascular encefálico e infarto agudo do miocárdio em pacientes com LES.