Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population.
Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors.
Corella
Dolores
D
Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain. dolores.corella@uv.es
Carrasco
Paula
P
Fitó
Montserrat
M
Martínez-González
Miguel Angel
MA
Salas-Salvadó
Jordi
J
Arós
Fernando
F
Lapetra
José
J
Guillén
Marisa
M
Ortega-Azorín
Carolina
C
Warnberg
Julia
J
Fiol
Miquel
M
Ruiz-Gutierrez
Valentina
V
Serra-Majem
Lluís
L
Martínez
J Alfredo
JA
Ros
Emilio
E
Estruch
Ramón
R
D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D004041:Dietary Fats; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008019:Life Style; D008297:Male; D019083:Mediterranean Region / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004041:Dietary Fats