Polimorfismos genéticos envolvidos na metabolização/detoxificação em Lúpus eritematoso

Abstract

Introduction. The development of clinical manifestations in patients with systemic lupus erythematosus (SLE) may involve an imbalance of redox by intense oxidative stress at cellular level. However, few studies have demonstrated the genetic role of oxidative metabolism in the development of symptoms in SLE. Objective. The aim of this investigation was to correlate the polymorphisms in genes of the enzymes glutathione S-transferase M1, T1 and P1 (Ile05Val /442-16C>T), superoxide dismutase (Ala16Val) and catalase (C-262T) with SLE. Methodology. Only women were recruited, 151 patients diagnosed with SLE treated at rheumatology service in Araujo Lima outpatient clinics, School of Medicine, Universidade Federal do Amazonas (UFAM) and 139 controls, no smoking, no symptoms of inflammation, without any disease and/or factors that change their oxidative stress state. Results. Thiol levels are decreased in SLE patients (p <0.001), while MDA levels were significantly higher (p <0.001). Patients with double null deletion T1null/M1null had a frequency six times higher than the controls (p <0.001, OR 3.6, CI 2.8-13.2). Patients had a lower frequency of SOD2 wild allele Ala/Ala compared to controls (13.8% vs 25.5%). Statistical significances were observed on the association between the double deletion T1null/M1null and mutants of the Ile105Val (p = 0.003, OR 0.14, CI 0.03- 0.56), 442-16C>T (p=0.008, OR 0.08, CI 0.01-0.70) and Ala16Val (p= 0.003, OR 0.14, CI 0.03-0.53). The same was observed between Ile105Val and 442-16C>T associated with mutant Ala16Val genotypes (p=0.038, OR 0.28, CI 0.08-0.91) and (p=0.024, OR 0.36, CI 0.15-0.87) respectively. Conclusion. The double null deletion T1null/M1null may contribute to the increased of the oxidative stress in SLE due to deficiency in xenobiotics detoxification. Isolated P1 and CAT polymorphisms do not seem to influence the increased oxidative stress in these patients, neither SLE clinical manifestations. Individuals with SLE carriers of the mutant SOD Val allele may have greater oxidative stress due to structural change in the protein and decreased H2O2 production. The combination of polymorphic genes may be involved in the pathogenesis of the disease through a combination of mechanisms that increase oxidative stress.