Cited by 63Glutathione Transferases and PolymorphismsParaoxonase enzyme and polymorphismsAntioxidant Activity and Oxidative Stress

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

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Mohammedi, Kamel, Bellili-Muñoz, Naïma, Marklund, Stefan L, Driss, Fathi, Le Nagard, Hervé, Patente, Thiago A, Fumeron, Frédéric, Roussel, Ronan +3 more·2015·Cardiovascular Diabetology

Abstract

BACKGROUND: Oxidative 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: The 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.

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  • The T-allele of rs2284659 in the promoter region of SOD3 has been related to a safer plasma redox balance, leading to an improvement in cardiovascular outcome in patients with type 2 diabetes.

    “Interestingly, the T-allele of rs2284659 in the promoter region of SOD3 has been related to a safer plasma redox balance, leading to an improvement in the cardiovascular outcome in patients with type 2 diabetes [42].”

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Authors
Mohammedi, K., Bellili-Muñoz, N., Marklund, S. L., Driss, F., Le Nagard, H., Patente, T. A., Fumeron, F., Roussel, R., Hadjadj, S., Marre, M., & Velho, G.
Affiliations
  • Inserm (FR)
  • Umeå University (SE)
Corresponding author
Velho, Gilberto
Venue
Cardiovascular Diabetology
Published
2015-01-15
Volume
14
Issue
1
Pages
845-845
ISSN
1475-2840 (ISSN-L)
OpenAlex
W2106812076
Cited by
63
References
45
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 13 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 2
FWCI
1.91
Type
journal article
Language
en
Open access
Locations
  • Cardiovascular Diabetology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • Fundação de Amparo à Pesquisa do Estado de São Paulo
  • Association Diabète Risque Vasculaire
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
extracellular superoxide dismutase, single nucleotide polymorphisms, myocardial infarction, all-cause mortality, cardiovascular mortality, oxidative stress, advanced oxidation protein products, isoprostanes, type 1 diabetes, type 2 diabetes, diabetic vascular complications, antioxidant enzymes, genetic susceptibility, plasma biomarkers
MeSH terms
Adult, Alleles, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Male, Middle Aged, Mortality, Myocardial Infarction, Prospective Studies, Risk Factors, Superoxide Dismutase, Genetic Variation, Cohort Studies, Biomarkers, Extracellular Fluid

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