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.
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.
Corella
Dolores
D
Genetic and Molecular Epidemiology Unit, Department of Preventive Medicine, School of Medicine, University of Valencia, Valencia, Spain. dolores.corella@uv.es
Carrasco
Paula
P
Amiano
Pilar
P
Arriola
Larraitz
L
Chirlaque
María Dolores
MD
Huerta
José María
JM
Martínez
Carmen
C
Martinez-Camblor
Pablo
P
Molina
Esther
E
Navarro
Carmen
C
Quirós
Juan R
JR
Rodríguez
Laudina
L
Sánchez
María José
MJ
Ortega-Azorín
Carolina
C
Ros
Emilio
E
Sala
Nuria
N
González
Carlos A
CA
Moreno
Concepción
C
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
D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL