Tese
Polimorfismo da Ala16Val MnSOD na hipercolesterolemia e sua associação com biomarcadores de inflamação e estresse oxidativo
Fecha
2010-03-11Registro en:
DUARTE, Marta Maria Medeiros Frescura. Ala16Val MnSOD polymorphism in the hypercholesterolemia and its association with inflammation biomarkers and oxidative stress. 2010. 148 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2010.
Autor
Duarte, Marta Maria Medeiros Frescura
Institución
Resumen
This study aimed to analyze the association between the genetic polymorphism of the manganese-dependent superoxide dismutase (Ala16Val MnSOD) and the oxidative and inflammatory markers in hypercholesterolemic and control individuals. Cholesterol levels in the control group were 104 to 178 mg/dL (2.69 4.61 mmol/L), while the hypercholesterolemic group presented levels 250 to 529 mg/dL (6.47 13.70 mmol/L).. The following biomarkers were also investigated: cholesterol-LDL oxidized (ox-LDL), antibodies anti-LDL oxidized (Anti-ox-LDL), ultra-sensitive C reactive protein (us-CRP), thiobarbituric acid reactive substances (TBARS), carbonyl protein, thiol groups, glutathione (GSH), Vitamins C and E, as well as the superoxide dismutase antioxidant enzymes (SOD) and catalasis (CAT). Additionally, we evaluated the levels of ischemia-modified albumin (IMA), as well as the lipid profile. IMA levels were higher in the hypercholesterolemic group and a significant association between hypercholesterolemia and ox-LDL, Anti-ox-LDL, IMA and us-CRP was observed. A negative correlation between HDL and us-CRP was observed as well. Ala16Val polymorphism influenced the oxidative and inflammatory markers
and HDL cholesterol levels were lower in the hypercholesterolemic individuals with the allele V (VV + AV). The present study demonstrated a positive correlation
between the total cholesterol levels, TBARS, carbonyl protein and thiol groups. In the hypercholesterolemic individuals there was a reduction in the GSH levels and in the SOD activity, probably due to the enzyme inactivation caused by the protein oxidation. The CAT activity significantly increased probably to partially compensate
the oxidative stress. An increase in the Vitamin E serum levels was also observed in the hypercholesterolemic individuals. The group with hypercholesterolemia presented
an increase of the oxidative stress, especially for the individuals with a VV genotype to Ala16Val MnSOD polymorphism. TBARS levels, carbonyl protein, thiols groups, Vitamin E and the catalasis activity were significantly higher in the hypercholesterolemic individuals with a VV genotype while GSH and SOD were lower
in these individuals. Functionally, the Val MnSOD variant reduces the MnSOD efficiency thus increasing the probability of development of endothelial dysfunction
and contributing to the increase in the risk of cardiovascular events, especially when associated to hypercholesterolemia states.
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