RESUMO
BACKGROUND: In diabetic retinopathy, the vascular endothelium is damaged due to oxidative stress and inflammation, and vitreous VEGF concentration becomes elevated. The association of diabetic retinopathy with single nucleotide polymorphisms (SNPs) was studied on two genes: VEGF, an important mediator of neovascularisation, and MnSOD, a major antioxidant enzyme. METHODS: The study population was 755 individuals consisting of 131 diabetic (type 1 or type 2) patients with diabetic retinopathy (DR group), 98 diabetic controls without retinopathy (DC group) and 526 non-diabetic controls. VEGF SNPs rs699947, rs2010963, rs2146232, rs3025033, rs3025039 and Ala16Val polymorphism of the MnSOD gene were genotyped. RESULTS: The frequencies of allele and genotype of the single genotyped VEGF SNPs or reconstructed haplotypes of these single SNPs did not differ between DR and DC groups. A higher frequency of the AlaAla genotype (p = 0.03) and Ala16 allele (p = 0.04) of the MnSOD gene in the DR group was found when compared with the DC group. CONCLUSIONS: In conclusion, the studied VEGF SNPs were not associated with the risk of diabetic retinopathy, and so it is unlikely that the VEGF gene is a major locus determining the risk of diabetic retinopathy. A statistically significant association of MnSOD Ala16Val polymorphism with diabetic retinopathy was found.
Assuntos
Retinopatia Diabética/genética , Polimorfismo de Nucleotídeo Único , Superóxido Dismutase/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Retinopatia Diabética/metabolismo , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/análise , Corpo Vítreo/químicaRESUMO
AIMS: Recent studies suggest the importance of oxidant stress in the progression of pulmonary fibrosis. The aim of this study was to investigate extracellular superoxide dismutase (ECSOD), the major antioxidant enzyme of the extracellular matrix of human lung, in biopsy-proven idiopathic pulmonary fibrosis (IPF) related to usual interstitial pneumonia (UIP). METHODS AND RESULTS: Fibrotic areas and fibroblastic foci in UIP lungs were notable for absence of ECSOD by immunohistochemistry. Western blotting showed significantly lowered immunoreactivity of ECSOD in fibrotic compared with non-fibrotic areas of the diseased lung. The only cell type that showed intense ECSOD positivity in UIP was the interstitial mast cell. In order to investigate the mechanism for ECSOD depletion in fibrotic areas, alveolar epithelial cells were exposed to tumour necrosis factor-alpha and transforming growth factor (TGF)-beta1; TGF-beta suggested a trend towards decreased synthesis. Patients with UIP were also assessed to determine whether this disease is associated with a naturally occurring mutation in ECSOD (Arg213Gly) which leads to a loss of tissue binding of ECSOD. No significant differences could be found in the allele or genotype frequencies of this polymorphism between 63 UIP patients and 61 control subjects. CONCLUSION: Overall, consistent with several other antioxidant enzymes, ECSOD is very low in fibrotic areas of UIP, which may further increase the oxidant burden in this disease.
