Polimorfismo da Ala16Val MnSOD em portadores do traço falciforme e sua associação com biomarcadores de estresse oxidativo

Abstract

Sickle cell trait (SCT) is the heterozygote of sickle cell anemia (HbAS), which carries the asymptomatic S gene and is considered clinically normal. Epidemiological studies show its high prevalence in the overall Brazilian population, and in certain cities such as Rio Grande do Sul, where a frequency of 1:75 is estimated. Recent studies have pointed out that the SCT because it represents approximately 40% of hemoglobin S (HbS), is involved with oxidative stress, which can act in the progression of the disease. Superoxide dismutase (SOD) is an antioxidant enzyme that may have decreased activity in some pathologies. The most common MnSOD polymorphism is Ala16Val, which is the result of a mutation that replaces the original GCT (alanine) codon for GTT (valine). The valine allele (V) hinders the transport and entry of the enzyme into the mitochondria, thereby both reducing the antioxidant capacity of the individual and favoring oxidative stress pathways. The aim of this study is to analyze the presence of the Ala16Val MnSOD polymorphism in patients with SCT and to associate it with biomarkers of oxidative stress. The study participants were recruited from the Blood Bank of the Santa Casa de Caridade Hospital of Uruguaiana. A total of 102 individuals were enrolled, 50 in the control group and 52 in the SCT group. After obtaining written informed consent, venous blood was collected. For each one, two tubes containing EDTA were collected for hematological, genomic, and oxidative stress analyses. The results showed that sickle cell carriers exhibit significantly decreased (p < 0.001) catalase, superoxide dismutase, and glutathione peroxidase activities compared with the control group. The same was also observed for the levels of antioxidant compounds such as glutathione, vitamin C, and total antioxidant status (p < 0.001). However, patients with SCT presented a statistically significant increase (p < 0.001) in oxidative damage to biomolecules such as protein carbonylation, lipid peroxidation, and DNA. Analysis of the Ala16Val MnSOD polymorphism showed 100% of the AV genotype in the control group, and 21% of the AA genotype and 79% of the AV genotype in the HbAS group. Although the current study could not associate the polymorphism with oxidative stress biomarkers, it suggested the SCT increased oxidative stress, and the Ala16Val MnSOD polymorphism was not associated with the parameters analyzed. However, because this study is the first to report these findings regarding the Ala16Val MnSOD polymorphism, it is expected that in a larger HbAS population, it will be possible to gain a better understanding of this genetic alteration.