Talmud, PJ; Stephens, JW; Hawe, E; Demissie, S; Cupples, LA; Hurel, SJ; ... Ordovas, JM; + view all Talmud, PJ; Stephens, JW; Hawe, E; Demissie, S; Cupples, LA; Hurel, SJ; Humphries, SE; Ordovas, JM; - view fewer (2005) The significant increase in cardiovascular disease risk in APOE epsilon 4 carriers is evident only in men who smoke: Potential relationship between reduced antioxidant status and ApoE4. ANN HUM GENET , 69 613 - 622. 10.1111/j.1529-8817.2005.00205.x.
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Data from 1668 men (316 cardiovascular disease events) from the Framingham Offspring Study was reanalysed, specifically examining APOE:smoking interactions. Overall hazard ratio (HR) for smoking was 1.95 (1.52, 2.50) compared to non-smokers. Using epsilon 3/3 as a referent group, in non-smokers HRs for epsilon 2 carriers (epsilon 2+; 1.04 (0.61, 1.76) and epsilon 4 carriers (epsilon 4+; 1.04 (0.70, 1.54) showed no major risk increase. In smokers, HRs were 1.96 (1.26, 2.78) in epsilon 3 epsilon 3 men, 3.46 (2.14, 5.60; p = 0.09 for interaction) in epsilon 2+ and 3.81 (2.49, 5.84; p = 0.01 for interaction), with a significant interaction between daily cigarette consumption and APOE genotype on risk (p = 0.03). The potential mechanism for this APOE epsilon 4:smoking interaction was examined in a second study of 728 Caucasian patients with diabetes, where markers of reactive oxygen species were available. APOE genotype was not associated with plasma OX-LDL or total antioxidant status (TAOS) in non-smokers. However, in smokers epsilon 4+ had 26.7% higher plasma OX-LDL than other genotypes (APOE:smoking interaction p = 0.04), while epsilon 2+ had 28.4% higher plasma TAOS than epsilon 3 epsilon 3 and epsilon 4+ combined (APOE:smoking interaction p = 0.026). Although direct extrapolation needs to be considered with caution, these results identify that the cardiovascular disease risk-raising effect of epsilon 4+ is confined to smokers, and a feasible mechanism is presented by the reduced antioxidant capacity/increased OX-LDL of apoE4.
|Title:||The significant increase in cardiovascular disease risk in APOE epsilon 4 carriers is evident only in men who smoke: Potential relationship between reduced antioxidant status and ApoE4|
|Keywords:||TAOS, apolipoprotein E, cardiovascular diseases, diabetes mellitus, gene, environment interaction, smoking, CORONARY-HEART-DISEASE, APOLIPOPROTEIN-E POLYMORPHISM, E GENOTYPE, HEALTHY-MEN, ATHEROSCLEROSIS, ASSOCIATION, OXIDATION, METAANALYSIS, PHENOTYPE, MORTALITY|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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