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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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].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [42]
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Self-citation
- 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
- ORCID
- Venue
- Cardiovascular Diabetology
- Published
- 2015-01-15
- Volume
- 14
- Issue
- 1
- Pages
- 845-845
- ISSN
- 1475-2840 (ISSN-L)
- PMC
- PMC4324771
- 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
- gold
- doi.org
- 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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