Edwards K L, Mahaney M C, Motulsky A G, Austin M A
Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle 98195, USA.
Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2456-64. doi: 10.1161/01.atv.19.10.2456.
The interrelationships among low density lipoprotein (LDL) particle size, plasma triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) are well established and may involve underlying genetic influences. This study evaluated common genetic effects on LDL size, TG, and HDL-C by using data from 85 kindreds participating in the Genetic Epidemiology of Hypertriglyceridemia (GET) Study. A multivariate, maximum likelihood-based approach to quantitative genetic analysis was used to estimate the additive effects of shared genes and shared, unmeasured nongenetic factors on variation in LDL size and in plasma levels of TG and HDL-C. A significant (P<0.001) proportion of the variance in each trait was attributable to the additive effects of genes. Maximum-likelihood estimates of heritability were 0.34 for LDL size, 0.41 for TG, and 0.54 for HDL-C. Significant (P<0.001) additive genetic correlations (rho(G)), indicative of the shared additive effects of genes on pairs of traits, were estimated between all 3 trait pairs: for LDL size and TG rho(G)=-0.87, for LDL size and HDL-C rho(G)=0.65, and for HDL-C and TG rho(G)=-0.54. A similar pattern of significant environmental correlations between the 3 trait pairs was also observed. These results suggest that a large proportion of the well-documented correlations in LDL size, TG, and HDL-C are likely attributable to the influence of the same gene(s) in these families. That is, the gene(s) that may contribute to decreases in LDL size also contribute significantly to higher plasma levels of TG and lower plasma levels of HDL-C. These relationships may be useful in identifying genes responsible for the associations between these phenotypes and susceptibility to cardiovascular disease in these families.
低密度脂蛋白（LDL）颗粒大小、血浆甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）之间的相互关系已得到充分证实，可能涉及潜在的遗传影响。本研究利用参与高甘油三酯血症遗传流行病学（GET）研究的85个家族的数据，评估了对LDL大小、TG和HDL-C的常见遗传效应。采用基于多变量、最大似然法的定量遗传分析方法，估计共享基因和共享的、未测量的非遗传因素对LDL大小以及TG和HDL-C血浆水平变异的加性效应。每个性状变异的很大一部分（P<0.001）可归因于基因的加性效应。LDL大小的遗传力最大似然估计值为0.34，TG为0.41，HDL-C为0.54。在所有3对性状之间均估计出显著（P<0.001）的加性遗传相关性（rho(G)），表明基因对性状对具有共享的加性效应：LDL大小与TG之间rho(G)= -0.87，LDL大小与HDL-C之间rho(G)= 0.65，HDL-C与TG之间rho(G)= -0.54。在这3对性状之间也观察到了类似的显著环境相关性模式。这些结果表明，LDL大小、TG和HDL-C中大量已被充分记录的相关性可能归因于这些家族中相同基因的影响。也就是说，可能导致LDL大小减小的基因也对较高的血浆TG水平和较低的血浆HDL-C水平有显著贡献。这些关系可能有助于识别在这些家族中负责这些表型与心血管疾病易感性之间关联的基因。
