TY - JOUR
T1 - CETP genotypes and HDL-cholesterol phenotypes in the HERITAGE Family Study
AU - Spielmann, Nadine
AU - Leon, Arthur S.
AU - Rao, D. C.
AU - Rice, Treva
AU - Skinner, James S.
AU - Bouchard, Claude
AU - Rankinen, Tuomo
PY - 2007/9/19
Y1 - 2007/9/19
N2 - Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c, HDL2-c, HDL3-c, and apolipoprotein (apo)A1 levels were measured, and 13 CETP single nucleotide polymorphisms (SNPs) were genotyped in 265 blacks and 486 whites. Three haplotypes defined by SNPs at the -1337, -971, and -629 sites were strongly associated with baseline HDL-c levels in whites. Both C-1337T and C-629A were associated with baseline HDL-c (P < 0.001) and apoA1 (P < 0.01) when tested separately. However, only C-629A remained significant in a combined model. G-971A was not associated with HDL phenotypes, but showed significant interactions with C-629A (P = 0.002) on baseline traits. Genotype-by-sex interactions were observed at the -629 locus for HDL3-c (P = 0.004) and apoA1 (P = 0.02) training responses in whites. In women, the -629 A/A homozygotes showed greater increases in HDL 3-c (P = 0.02) and apoA1 (P = 0.02) levels than the other genotypes. Finally, apolipoprotein E (APOE) genotype and the CETP C-629A locus contributed independently and in additive fashion to the HDL traits, explaining 6.0-8.8% of the variance. The CETP -1337T and -629A alleles are associated with higher baseline HDL-c and apoA1 levels. The beneficial effects of endurance training on plasma HDL3-c and apoA1 levels are evident in white women homozygous for the -629A allele. The CETP and APOE genotypes account for up to 9% of the variance in HDL-c phenotypes in the HERITAGE Family Study.
AB - Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c, HDL2-c, HDL3-c, and apolipoprotein (apo)A1 levels were measured, and 13 CETP single nucleotide polymorphisms (SNPs) were genotyped in 265 blacks and 486 whites. Three haplotypes defined by SNPs at the -1337, -971, and -629 sites were strongly associated with baseline HDL-c levels in whites. Both C-1337T and C-629A were associated with baseline HDL-c (P < 0.001) and apoA1 (P < 0.01) when tested separately. However, only C-629A remained significant in a combined model. G-971A was not associated with HDL phenotypes, but showed significant interactions with C-629A (P = 0.002) on baseline traits. Genotype-by-sex interactions were observed at the -629 locus for HDL3-c (P = 0.004) and apoA1 (P = 0.02) training responses in whites. In women, the -629 A/A homozygotes showed greater increases in HDL 3-c (P = 0.02) and apoA1 (P = 0.02) levels than the other genotypes. Finally, apolipoprotein E (APOE) genotype and the CETP C-629A locus contributed independently and in additive fashion to the HDL traits, explaining 6.0-8.8% of the variance. The CETP -1337T and -629A alleles are associated with higher baseline HDL-c and apoA1 levels. The beneficial effects of endurance training on plasma HDL3-c and apoA1 levels are evident in white women homozygous for the -629A allele. The CETP and APOE genotypes account for up to 9% of the variance in HDL-c phenotypes in the HERITAGE Family Study.
KW - Exercise training
KW - Family study
KW - High-density lipoprotein-cholesterol
KW - Single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=34548837731&partnerID=8YFLogxK
U2 - 10.1152/physiolgenomics.00281.2006
DO - 10.1152/physiolgenomics.00281.2006
M3 - Article
C2 - 17519358
AN - SCOPUS:34548837731
SN - 1094-8341
VL - 31
SP - 25
EP - 31
JO - Physiological genomics
JF - Physiological genomics
IS - 1
ER -