Apolipoprotein E (APOE) genotype unlikely to affect smoker's CV risk

The authors investigated the effect of the APOE genotype on the risk of coronary disease due to smoking using patients from the International Study of Infarct Survival (ISIS) genetic case control study. The ISIS study collected blood from patients presenting within 24 hours of the onset of suspected acute myocardial infarction. A few months after discharge from hospital, information was sought from surviving cases about aspects of their lifestyle (including smoking habits). A similar questionnaire was then sent to each patient's siblings (and their spouses) and children older than 30 years. Blood samples were then obtained from those who had completed the questionnaire. APOE genotype was established in 4484 patients with acute MI before the age of 55 years for men and 65 years for women, and also in 5757 controls with no history of cardiovascular disease. On average, the MI hazard ratio was 1.17 per stepwise change from є3/2 to є3/3 to є3/4 genotype and was only slightly changed when the comparison was restricted from to the 3460 controls selected by marriage alone. For individuals in the study who had a known smoking status, the hazard ratio for MI in smokers compared with non-smokers was 4.6 (4.2-5.1). The researchers found, however, that there was no significant difference between smoker and non-smoker hazard ratios for the different APOE genotype. Commenting on their findings, Keavney et al stated: "Unjustified claims that smoking is importantly cardiotoxic only for carriers of particular genotypes could obviously be hazardous".They suggest a reliable assessment of any gene-environment interaction that may exist is likely to require studies with large numbers of disease cases and the avoidance of undue emphasis on selected subgroups. Reference...