title: Smoking, apolipoprotein E genotypes, and mortality (the Ludwigshafen RIsk and Cardiovascular Health study).
abstract: OBJECTIVE
  The genetic polymorphism of apolipoprotein E (APOE) has been suggested to modify the effect of smoking on the development of coronary artery disease (CAD) in apparently healthy persons. The interaction of these factors in persons undergoing coronary angiography is not known.
  
  
  RESULTS
  We analysed the association between the APOE-genotype, smoking, angiographic CAD, and mortality in 3263 participants of the LUdwigshafen RIsk and Cardiovascular Health study. APOE-genotypes were associated with CAD [ε22 or ε23: odds ratio (OR) 0.56, 95% confidence interval (CI) 0.43-0.71; ε24 or ε34 or ε44: OR 1.10, 95% CI 0.89-1.37 compared with ε33] and moderately with cardiovascular mortality [ε22 or ε23: hazard ratio (HR) 0.71, 95% CI 0.51-0.99; ε33: HR 0.92, 95% CI 0.75-1.14 compared with ε24 or ε34 or ε44]. HRs for total mortality were 1.39 (95% CI 0.39-0.1.67), 2.29 (95% CI 1.85-2.83), 2.07 (95% CI 1.64-2.62), and 2.95 (95% CI 2.10-4.17) in ex-smokers, current smokers, current smokers without, or current smokers with one ε4 allele, respectively, compared with never-smokers. Carrying ε4 increased mortality in current, but not in ex-smokers (HR 1.66, 95% CI 1.04-2.64 for interaction). These findings applied to cardiovascular mortality, were robust against adjustment for cardiovascular risk factors, and consistent across subgroups. No interaction of smoking and ε4 was seen regarding non-cardiovascular mortality. Smokers with ε4 had reduced average low-density lipoprotein (LDL) diameters, elevated oxidized LDL, and lipoprotein-associated phospholipase A2.
  
  
  CONCLUSIONS
  In persons undergoing coronary angiography, there is a significant interaction between APOE-genotype and smoking. The presence of the ε4 allele in current smokers increases cardiovascular and all-cause mortality.
authors: Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, D-68167 Mannheim, Germany. tanja.grammer@medma.uni-heidelberg.de
authors: Tanja B
authors: TB
authors: Grammer
authors: Michael M
authors: MM
authors: Hoffmann
authors: Hubert
authors: H
authors: Scharnagl
authors: Marcus E
authors: ME
authors: Kleber
authors: Günther
authors: G
authors: Silbernagel
authors: Stefan
authors: S
authors: Pilz
authors: Andreas
authors: A
authors: Tomaschitz
authors: Elisabeth
authors: E
authors: Lerchbaum
authors: Rüdiger
authors: R
authors: Siekmeier
authors: Winfried
authors: W
authors: März
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D002423:Cause of Death; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D012307:Risk Factors; D012907:Smoking / Q000235:genetics* / Q000401:mortality
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E
keywords: Apolipoprotein E; C-reactive protein; Coronary artery disease; Genotype; Inflammation