Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetesReport as inadecuate




Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes - Download this document for free, or read online. Document in PDF available to download.

Cardiovascular Diabetology

, 14:845

First Online: 15 January 2015Received: 11 September 2014Accepted: 10 December 2014

Abstract

BackgroundOxidative stress is involved in development of diabetes complications. Extracellular superoxide dismutase EC-SOD, SOD3 is a major extracellular antioxidant enzyme and is highly expressed in arterial walls. Advanced oxidation protein products AOPP and 8-iso-prostaglandin isoprostane are markers of oxidative stress. We investigated association of SOD3 gene variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial infarction and mortality in diabetic patients.

MethodsWe studied three cohorts designed to evaluate the vascular complications of diabetes: the GENEDIAB study 469 participants with type 1 diabetes at baseline; follow-up data for 259 participants, the GENESIS study 603 participants with type 1 diabetes at baseline; follow-up data for 525 participants and the DIABHYCAR study 3137 participants with type 2 diabetes at baseline and follow-up. Duration of follow-up was 9, 5, and 5 years, respectively. Main outcome measures were incidence of myocardial infarction, and cardiovascular and total mortality during follow-up. Six single nucleotide polymorphisms in the SOD3 locus were genotyped in the three cohorts. Plasma concentrations of EC-SOD, AOPP, and isoprostane were measured in baseline samples of GENEDIAB participants.

ResultsIn GENEDIAB-GENESIS pooled cohorts, the minor T-allele of rs2284659 variant was inversely associated with the prevalence at baseline Odds Ratio 0.48, 95% CI 0.29–0.78, p = 0.004 and the incidence during follow-up of myocardial infarction Hazard Ratio 0.58, 95% CI 0.40–0.83, p = 0.003 and with cardiovascular HR 0.33, 95% CI 0.08–0.74, p = 0.004 and all-cause mortality HR 0.44, 95% CI 0.21–0.73, p = 0.0006. The protective allele was associated with higher plasma EC-SOD and lower plasma AOPP concentrations in GENEDIAB. It was also inversely associated with incidence of myocardial infarction HR 0.75, 95% CI 0.59–0.94, p = 0.01 and all-cause mortality HR 0.87, 95% CI 0.79–0.97, p = 0.008 in DIABHYCAR.

ConclusionsThe T-allele of rs2284659 in the promoter of SOD3 was associated with a more favorable plasma redox status and with better cardiovascular outcomes in diabetic patients. Our results suggest that EC-SOD plays an important role in the mechanisms of vascular protection against diabetes-related oxidative stress.

KeywordsOxidative Stress SOD3 Myocardial Infarction Mortality Diabetes Mellitus AbbreviationsACEAngiotensin converting enzyme

ANCOVAAnalysis of covariance

ANOVAAnalysis of variance

AOPPAdvanced oxidation protein products

BMIBody mass index

CIConfidence intervals

eGFREstimated glomerular filtration rate

EC-SODExtracellular superoxide dismutase

HRHazard ratio

MAFMinor allele frequency

MDRD-Modification of Diet in Renal Disease- formula

OROdds ratio

ROSReactive oxygen species

SNPSingle nucleotide polymorphism

SODSuperoxide dismutase

UAEUrinary albumin excretion

Electronic supplementary materialThe online version of this article doi:10.1186-s12933-014-0163-2 contains supplementary material, which is available to authorized users.

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Author: Kamel Mohammedi - Naïma Bellili-Muñoz - Stefan L Marklund - Fathi Driss - Hervé Le Nagard - Thiago A Patente - Frédér

Source: https://link.springer.com/article/10.1186/s12933-014-0163-2



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