title: Large-scale evidence that the cardiotoxicity of smoking is not significantly modified by the apolipoprotein E epsilon2/epsilon3/epsilon4 genotype.
abstract: Results from two small studies, involving a total of only 174 cases, have suggested that the increased risk of coronary heart disease conferred by cigarette smoking is substantially affected by genotype at the apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4 polymorphism. We have established APOE genotypes in 4484 patients with acute myocardial infarction diagnosed before the age of 55 years for male and 65 years for female patients, and in 5757 controls with no history of cardiovascular disease. On average, the hazard ratio for myocardial infarction was 1.17 (95% CI 1.09-1.25; p<0.00001) per stepwise change from epsilon3/2 to epsilon3/3 to epsilon3/4 genotype. Among individuals in this study with known cigarette smoking status, the hazard ratio for myocardial infarction in smokers versus non-smokers was 4.6 (4.2-5.1). There was, however, no significant difference between the smoker/non-smoker hazard ratios for those with different APOE genotypes (chi2(2)=0.69; p=0.7). When differences in risk between different genotypes are not extreme (as with this APOE polymorphism), reliable assessment of hypothesised gene-environment interactions will often require the study of many thousands of disease cases.
authors.affiliation: Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. b.d.keavney@ncl.ac.uk
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
authors.forename: Sarah
authors.initials: S
authors.lastname: Parish
authors.forename: Alison
authors.initials: A
authors.lastname: Palmer
authors.forename: Sarah
authors.initials: S
authors.lastname: Clark
authors.forename: Linda
authors.initials: L
authors.lastname: Youngman
authors.forename: John
authors.initials: J
authors.lastname: Danesh
authors.forename: Colin
authors.initials: C
authors.lastname: McKenzie
authors.forename: Marc
authors.initials: M
authors.lastname: Delépine
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Richard
authors.initials: R
authors.lastname: Peto
authors.forename: Rory
authors.initials: R
authors.lastname: Collins
mesh_terms: D000368:Aged; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E