Survival of atherosclerotic patients as related to oxidative stress and gene polymorphisms.
A prospective molecular epidemiology study was implemented in a cohort of 98 subjects suffering from severe atherosclerotic lesions requiring removal of an abdominal aorta fragment. We previously published the results relative to detection, in the aorta medium layer, of bulky DNA adducts and fluorescent polycyclic aromatic hydrocarbon-related DNA adducts, oxidative DNA damage, and mitochondrial DNA 4977 common deletion, as well as GSTM1 and GSTT1 gene polymorphisms. We report herein new data, relative to oxidative stress biomarkers, including oxidative DNA damage in both inner and medium aorta layers, malondialdehyde in the medium layer, homocysteine and reduced glutathione in plasma, and those relative to additional gene polymorphisms, including NAT1, NAT2, OGG1, MTHFR, Leiden factor V, and prothrombin. The results of biochemical and molecular analyses were related to survival of the patients, whose average age was 70 at the start of the follow up. During the following 14 years, 71.4% of them died. The results obtained provide evidence for the crucial impact of oxidative stress and certain gene polymorphisms on clinical and biochemical patterns as well as on survival of patients. Survival was significantly affected not only by traditional risk factors for atherosclerosis but also by molecular end-points and adverse gene polymorphisms, and by their combinations.
Izzotti
Alberto
A
Department of Health Sciences, University of Genoa, via A. Pastore 1, I-16132 Genoa, Italy. izzotti@unige.it
Piana
Antonietta
A
Minniti
Giuseppe
G
Vercelli
Marina
M
Perrone
Lucia
L
De Flora
Silvio
S
D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D004249:DNA Damage; D005500:Follow-Up Studies; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D053208:Kaplan-Meier Estimate; D018384:Oxidative Stress / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies
D015415:Biomarkers; D006710:Homocysteine; D005978:Glutathione