Spielmann Nadine, Leon Arthur S, Rao D C, Rice Treva, Skinner James S, Bouchard Claude, Rankinen Tuomo
Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808-4124, USA.
Physiol Genomics. 2007 Sep 19;31(1):25-31. doi: 10.1152/physiolgenomics.00281.2006. Epub 2007 May 22.
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, HDL(2)-c, HDL(3)-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 HDL(3)-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 HDL(3)-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.
在“遗传家庭研究”中，研究了胆固醇酯转运蛋白（CETP）基因多态性与耐力训练20周前后高密度脂蛋白胆固醇（HDL-c）水平之间的关联。测量了血浆HDL-c、HDL(2)-c、HDL(3)-c和载脂蛋白（apo）A1水平，并对265名黑人及486名白人的13个CETP单核苷酸多态性（SNP）进行了基因分型。由-1337、-971和-629位点的SNP定义的三种单倍型与白人的基线HDL-c水平密切相关。单独测试时，C-1337T和C-629A均与基线HDL-c（P < 0.001）和apoA1（P < 0.01）相关。然而，在联合模型中只有C-629A仍具有显著性。G-971A与HDL表型无关，但在基线特征上与C-629A存在显著交互作用（P = 0.002）。在白人中，观察到-629位点存在HDL(3)-c（P = 0.004）和apoA1（P = 0.02）训练反应的基因型-性别交互作用。在女性中，-629 A/A纯合子的HDL(3)-c（P = 0.02）和apoA1（P = 0.02）水平升高幅度大于其他基因型。最后，载脂蛋白E（APOE）基因型和CETP C-629A位点以独立且累加的方式对HDL特征产生影响，解释了6.0 - 8.8%的变异。CETP -1337T和-629A等位基因与较高的基线HDL-c和apoA1水平相关。耐力训练对血浆HDL(3)-c和apoA1水平的有益影响在-629A等位基因纯合的白人女性中很明显。在“遗传家庭研究”中，CETP和APOE基因型占HDL-c表型变异的比例高达9%。
