title: Common cholesteryl ester transfer protein gene variation related to high-density lipoprotein cholesterol is not associated with decreased coronary heart disease risk after a 10-year follow-up in a Mediterranean cohort: Modulation by alcohol consumption.
abstract: OBJECTIVE
  Despite the consistent association between cholesteryl ester transfer protein (CETP) gene variation and plasma HDL-C, huge controversy still rages on its association with coronary heart disease (CHD). We investigated the association between the CETP-TaqIB polymorphism, HDL-C and incident CHD in a Mediterranean population.
  
  
  METHODS
  A nested case-control study among participants of the Spanish EPIC cohort was performed. 41,440 healthy individuals (30-69 years) were followed up over a 10-year period, incident CHD cases being identified. We analyzed 557 confirmed CHD cases and 1180 healthy controls.
  
  
  RESULTS
  Despite B2B2 subjects having the highest HDL-C concentrations and B1B1, the lowest (P<0.001), no protective effect of the B2 allele against CHD incidence was observed. Thus, in comparison with B1B1 subjects, the adjusted CHD risk of B1B2 was OR: 1.00, 95% CI: 0.80-1.26; P=0.982, and that of B2B2 was OR: 1.16, 95% CI: 0.84-1.61; P=0.374. These results did not change after adjustment for HDL-C. No significant interaction between alcohol consumption and the CETP-TaqIB polymorphism in determining HDL-C was found. However, a different effect of this polymorphism on CHD risk in drinkers and non-drinkers was observed. In non-drinkers, the B2B2 genotype was associated with a non-significant lower CHD risk, whereas in drinkers it was associated with a greater risk (OR: 1.55, 95% CI: 1.05-2.29; P=0.026). We also observed that in diabetics (11% cases and 7.4% controls), the B2 allele was significantly associated with higher CHD risk.
  
  
  CONCLUSIONS
  In this Mediterranean population, the CETP-TaqIB polymorphism was not associated with a lower CHD incidence, and its effect was modulated by alcohol and possibly by diabetes.
authors.affiliation: Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine, School of Medicine, University of Valencia, Valencia, Spain. dolores.corella@uv.es
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Paula
authors.initials: P
authors.lastname: Carrasco
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.forename: Larraitz
authors.initials: L
authors.lastname: Arriola
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: José María
authors.initials: JM
authors.lastname: Huerta
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: Juan 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: Carolina
authors.initials: C
authors.lastname: Ortega-Azorín
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
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D019083:Mediterranean Region; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL