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.
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.
Corella
Dolores
D
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
Portolés
Olga
O
Arriola
Larraitz
L
Chirlaque
María Dolores
MD
Barrricarte
Aurelio
A
Francés
Francesc
F
Huerta
José María
JM
Larrañaga
Nerea
N
Martínez
Carmen
C
Martinez-Camblor
Pablo
P
Molina
Esther
E
Navarro
Carmen
C
Quirós
Jose R
JR
Rodríguez
Laudina
L
Sánchez
María José
MJ
Ros
Emilio
E
Sala
Nuria
N
González
Carlos A
CA
Moreno-Iribas
Concepción
C
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
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D005227:Fatty Acids