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

Abstract : AbstractBackgroundOxidative 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.
Type de document :
Article dans une revue
Cardiovascular Diabetology, BioMed Central, 2015, 14 (1), pp.845. 〈10.1186/s12933-014-0163-2〉
Liste complète des métadonnées

Littérature citée [44 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01264487
Contributeur : Bmc Bmc <>
Soumis le : vendredi 29 janvier 2016 - 12:42:44
Dernière modification le : mercredi 5 septembre 2018 - 13:30:10
Document(s) archivé(s) le : vendredi 11 novembre 2016 - 20:16:10

Fichiers

12933_2014_Article_163.pdf
Publication financée par une institution

Identifiants

Citation

Kamel Mohammedi, Naïma Bellili-Muñoz, Stefan Marklund, Fathi Driss, Hervé Le Nagard, et al.. 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. Cardiovascular Diabetology, BioMed Central, 2015, 14 (1), pp.845. 〈10.1186/s12933-014-0163-2〉. 〈inserm-01264487〉

Partager

Métriques

Consultations de la notice

272

Téléchargements de fichiers

120