Manganese superoxide dismutase dimorphism relationship with severity and prognosis in cardiogenic shock due to dilated cardiomyopathy.
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; p < 0.05) and hemodynamic support duration (144.6 vs Ala/Val-variant: 108.8 h and Ala/Ala-variant: 52.5 h; p < 0.05) with a positive correlation (Spearman rho = 0.72, p < 0.05). Moreover, Val/Val-variant significantly influenced the mortality (Spearman rho = 0.67, p < 0.05), 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.
AP-HP, Avicenne Hospital, Department of Cardiology, UFR SMBH Paris 13 University, Bobigny, France. jean-christophe.charniot@avc.aphp.fr
J C
JC
Charniot
A
A
Sutton
D
D
Bonnefont-Rousselot
C
C
Cosson
R
R
Khani-Bittar
P
P
Giral
N
N
Charnaux
J P
JP
Albertini
D000409:Alanine / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D015415:Biomarkers; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D011379:Prognosis; D011392:Proline / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index; D012770:Shock, Cardiogenic / Q000175:diagnosis / Q000201:enzymology* / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014633:Valine / Q000235:genetics / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
D000409:Alanine; D015415:Biomarkers; D005979:Glutathione Peroxidase; D007930:Leucine; D020097:Natriuretic Peptide, Brain; D011392:Proline; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D014633:Valine; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C000722067:GPX1 protein, human