Tang Weihong, Apostol George, Schreiner Pamela J, Jacobs David R, Boerwinkle Eric, Fornage Myriam
University of Minnesota, Minneapolis, USA.
Circ Cardiovasc Genet. 2010 Apr;3(2):179-86. doi: 10.1161/CIRCGENETICS.109.913426. Epub 2010 Feb 11.
Genome-wide association studies in European Americans have reported several single-nucleotide polymorphisms (SNPs) in the lipoprotein lipase gene associated with plasma levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides. However, the influences of the lipoprotein lipase SNPs on longitudinal changes of these lipids have not been systematically examined.
On the basis of data from 2045 African Americans and 2116 European Americans in the Coronary Artery Risk Development in Young Adults study, we investigated cross-sectional and longitudinal associations of lipids with 8 lipoprotein lipase SNPs, including the 2 that have been reported in genome-wide association studies. Plasma levels of HDL-C and triglycerides were measured at 7 examinations during 20 years of follow-up. In European Americans, rs328 (Ser447Stop), rs326, and rs13702 were significantly associated with cross-sectional interindividual variations in triglycerides and HDL-C (P<0.005) and with their longitudinal changes over time (P<0.05). The minor alleles in rs326, rs328, and rs13702 that predispose an individual to lower triglycerides and higher HDL-C levels at young adulthood further slow down the trajectory increase in triglycerides and decrease in HDL-C during 20 years of follow-up. In African Americans, these 3 SNPs were significantly associated with triglycerides, but only rs326 and rs13702 were associated with HDL-C (P<0.008). Rs328 showed a stronger association in European Americans than in African Americans, and adjustment for it did not remove all of the associations for the other SNPs. Longitudinal changes in either trait did not differ significantly by SNP genotypes in African Americans.
Our data suggest that aging interacts with LPL gene variants to influence the longitudinal lipid variations, and there is population-related heterogeneity in the longitudinal associations.
针对欧裔美国人的全基因组关联研究报告称，脂蛋白脂肪酶基因中的几个单核苷酸多态性（SNP）与高密度脂蛋白胆固醇（HDL-C）和甘油三酯的血浆水平相关。然而，脂蛋白脂肪酶SNP对这些脂质纵向变化的影响尚未得到系统研究。
基于青年成年人冠状动脉风险发展研究中2045名非裔美国人和2116名欧裔美国人的数据，我们研究了脂质与8个脂蛋白脂肪酶SNP的横断面和纵向关联，其中包括在全基因组关联研究中已报告的2个SNP。在20年的随访期间，通过7次检查测量了HDL-C和甘油三酯的血浆水平。在欧裔美国人中，rs328（Ser447Stop）、rs326和rs13702与甘油三酯和HDL-C的横断面个体间差异显著相关（P<0.005），并与它们随时间的纵向变化相关（P<0.05）。rs326、rs328和rs13702中的次要等位基因使个体在成年早期倾向于较低的甘油三酯水平和较高的HDL-C水平，在20年的随访期间，进一步减缓了甘油三酯的上升轨迹和HDL-C的下降轨迹。在非裔美国人中，这3个SNP与甘油三酯显著相关，但只有rs326和rs13702与HDL-C相关（P<0.008）。Rs328在欧裔美国人中的关联性比在非裔美国人中更强，对其进行调整并不能消除其他SNP的所有关联。非裔美国人中任一性状的纵向变化在SNP基因型之间没有显著差异。
我们的数据表明，衰老与LPL基因变异相互作用，影响脂质的纵向变化，并且纵向关联存在人群相关的异质性。
