title: Saturated fat intake and alcohol consumption modulate the association between the APOE polymorphism and risk of future coronary heart disease: a nested case-control study in the Spanish EPIC cohort.
abstract: The association is still not clear between the common APOE polymorphism and coronary heart disease (CHD) risk, nor its modulation by diet. Thus, our aim was to study the association between the APOE genotypes and incident CHD and how dietary fat and alcohol consumption modify these effects. We performed a nested case-control study in the Spanish European Prospective Investigation into Cancer and Nutrition cohort. Healthy men and women (41,440, 30-69 years) were followed up over a 10-year period, with the incident CHD cases being identified. We analyzed 534 incident CHD cases and 1123 controls. APOE, dietary intake and plasma lipids were determined at baseline. The APOE polymorphism was significantly associated with low-density lipoprotein cholesterol (LDL-C), and gene-alcohol interactions in determining LDL-C were detected. In the whole population, the E2 allele was significantly associated with a lower CHD risk than E3/E3 subjects [odds ratio (OR), 0.58; 95% confidence interval (CI), 0.38-0.89]. The E4 allele did not reach statistical significance vs. E3/E3 (OR, 1.17; 95% CI, 0.88-1.58). However, saturated fat intake modified the effect of the APOE polymorphism in determining CHD risk. When saturated fat intake was low (<10% of energy), no statistically significant association between the APOE polymorphism and CHD risk was observed (P=.682). However, with higher intake (≥10%), the polymorphism was significant (P=.005), and the differences between E2 and E4 carriers were magnified (OR for E4 vs. E2, 3.33; 95% CI, 1.61-6.90). Alcohol consumption also modified the effect of the APOE on CHD risk. In conclusion, in this Mediterranean population, the E2 allele is associated with lower CHD risk, and this association is modulated by saturated fat and alcohol consumption.
authors.affiliation: Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine, University of Valencia, Valencia and CIBER Fisiopatología de la Obesidad y Nutrición, ISCIII, Spain. dolores.corella@uv.es
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Olga
authors.initials: O
authors.lastname: Portolés
authors.forename: Larraitz
authors.initials: L
authors.lastname: Arriola
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barrricarte
authors.forename: Francesc
authors.initials: F
authors.lastname: Francés
authors.forename: José María
authors.initials: JM
authors.lastname: Huerta
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Camblor
authors.forename: Esther
authors.initials: E
authors.lastname: Molina
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Jose R
authors.initials: JR
authors.lastname: Quirós
authors.forename: Laudina
authors.initials: L
authors.lastname: Rodríguez
authors.forename: María José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.forename: Nuria
authors.initials: N
authors.lastname: Sala
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
authors.forename: Concepción
authors.initials: C
authors.lastname: Moreno-Iribas
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D004032:Diet; D005227:Fatty Acids / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D044465:White People
chemical_list: D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D005227:Fatty Acids