Manganese superoxide dismutase dimorphism relationship with severity and prognosis in cardiogenic shock due to dilated cardiomyopathy
| Autor: | N. Charnaux, C. Cosson, Jean-Christophe Charniot, P. Giral, Jean-Paul Albertini, Dominique Bonnefont-Rousselot, Angela Sutton, R. Khani-Bittar |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cardiomyopathy
Dilated Male medicine.medical_specialty Acute coronary syndrome Genotype Proline Heart disease Shock Cardiogenic Cardiomyopathy Biology medicine.disease_cause Protein oxidation Severity of Illness Index Biochemistry Gastroenterology Cohort Studies Glutathione Peroxidase GPX1 Leucine Internal medicine Natriuretic Peptide Brain medicine Humans Alleles Genetic Association Studies Glutathione Peroxidase Alanine Polymorphism Genetic Ejection fraction Superoxide Dismutase Cardiogenic shock Valine Dilated cardiomyopathy General Medicine Middle Aged Prognosis medicine.disease Surgery Oxidative Stress Female Reactive Oxygen Species Biomarkers Oxidative stress |
| Zdroj: | Free Radical Research. 45:379-388 |
| ISSN: | 1029-2470 1071-5762 |
| DOI: | 10.3109/10715762.2010.532792 |
| Popis: | The aim was to determine (a) Ala-16Val-SOD2 dimorphisms; (b) allelic frequency and phenotype of a common Pro-Leu polymorphism in GPx1, in a cohort of patients with a cardiogenic shock (CS) due to dilated cardiomyopathy without acute coronary syndrome. Consecutive patients with de novo CS that worsened a dilated (DCM) or ischemic (ICM) cardiomyopathy. Congenital heart disease, pacemaker and other shock aetiologies were excluded. To determine oxidative stress (OS), this study evaluated lipid peroxidation, protein oxidation and erythrocyte GPx, SOD and catalase activities. Ala16Val-SOD2 (dbSNP: rs4880) and Pro198Leu-GPx1 (dbSNP: rs1050450) polymorphisms were studied by allelic discrimination using fluorogenic probes and the 5'nuclease (TaqMan) assay. Twenty-four patients (with ICM (n = 8) or DCM (n = 16), age = 57.5 ± 10.7 years, LVEF = 25.3 ± 8.5%, NT-proBNP levels = 8540 ± 1703 ng/L) were included during a 15 month follow-up. OS parameters were significantly higher in patients than in controls. Distribution of MnSOD genotypes was 47% Val/Val-variant, 29.5% Ala/Val and 23.5% Ala/Ala-variants. Severity of CS was more important in patients with Val/Val-variant and can be put in parallel with NT-proBNP levels (Val/Val-variant: 11 310 ± 3875 ng/L vs Ala/Ala-variant: 6486 ± 1375 ng/L and Ala/Val-variant: 6004 ± 2228 ng/L; p0.05) and hemodynamic support duration (144.6 vs Ala/Val-variant: 108.8 h and Ala/Ala-variant: 52.5 h; p0.05) with a positive correlation (Spearman rho = 0.72, p0.05). Moreover, Val/Val-variant significantly influenced the mortality (Spearman rho = 0.67, p0.05), but not the morbidity (p = 0.3). Distribution of GPx genotypes was 64% Pro/Pro, 18% Pro/Leu and 18% Leu/Leu. GPx-variants influenced neither GPx activities nor cardiac events. In conclusion, CS was associated with markers of increased OS. GPx polymorphism did not influence the GPx activity. Only the Val-encoding MnSOD allele was significantly correlated with the severity and prognosis of CS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|