CETP C>->−629>A Genotypes and HDL-Cholesterol Phenotypes in the HERITAGE Family Study

PURPOSE: Physical activity is thought to improve high-density lipoprotein cholesterol (HDL-C) metabolism by enhancing reverse cholesterol transport (RCT). Plasma cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL particles to triglyceride-rich lipoproteins and is therefore considered a key protein in RCT. METHODS: The aim of this study was to investigate associations between the CETP C>-629>A gene polymorphism and HDL-C profile before and after a 20-week endurance training program in the HERITAGE Family Study. Plasma HDL-C, HDL2- C, HDL3-C and apolipoprotein (apo) A1 levels were measured in 265 Blacks (88 men, 177 women) and 486 Whites (237 men, 249 women). RESULTS: In whites, A/A homozygotes showed significantly higher baseline HDLC (p<0.001), HDL2-C (p<0.001), HDL3-C (p=0.01) and apo A1 (p<0.001) levels compared with C/A heterozygotes and C/C homozygotes. Similar patterns were found in Blacks for baseline HDL-C (p=0.06) and HDL2-C (p=0.004). Significant genotypebysex interactions were observed for HDL3-C (p<0.001) and apo A1 (p<0.002) training responses in Whites. In women, the A/A homozygotes showed greater training-induced increases in HDL3-C (p=0.02) and Apo A1 (p=0.02) levels than the other genotypes, whereas the training responses did not differ between the genotypes in males. The associations were independent of age, sex, baseline BMI and covariates such as smoking, alcohol, endogenous hormones, abdominal fat and plasma triglycerides. CONCLUSIONS: In summary, the CETP −629>A allele is strongly associated with higher baseline HDL-C. Additionally, the beneficial effects of endurance training on plasma HDL3-C and apo A1 levels are particularly evident in white women with the A/A genotype.