Abstract
The HDL and LDL subclass profile is an emerging cardiovascular risk factor. Yet, the biological and genetic mechanisms controlling the lipoprotein subclass distribution are unclear. Therefore, we aimed 1) to determine the heritability of the entire spectrum of LDL and HDL subclass features and 2) to identify gene loci influencing the lipoprotein subfraction pattern. Using NMR spectroscopy, we analyzed the lipoprotein subclass distribution in 1,275 coronary artery disease patients derived from the Regensburg Myocardial Infarction Family Study. We calculated heritabilities, performed a microsatellite genome scan, and calculated linkage. HDL and LDL subclass profiles showed heritabilities ranging from 23% to 67% (all P < 10(-3)) of traits using univariate calculation. After multivariate adjustment, we found heritabilities of 27-48% (all P < 0.05) for HDL and 21-44% for LDL traits. The linkage analysis revealed a significant logarithm of the odds (LOD) score (3.3) for HDL particle concentration on chromosome 18 and a highly suggestive signal for HDL particle size on chromosome 12 (2.9). After multivariate adjustment, we found a significant maximum LOD score of 3.7 for HDL size. Our study is the first to analyze heritability and linkage for the entire spectrum of LDL and HDL subclass features. Our findings may lead to the identification of genes controlling the lipoprotein subclass distribution.
Highlights
The HDL and LDL subclass profile is an emerging cardiovascular risk factor
LDL and HDL cholesterol levels have been established as important risk factors for coronary artery disease (CAD), and the decrease of LDL cholesterol is a principal target in cardiovascular preventive strategies [1]
We aimed 1) to determine the heritability of the entire spectrum of LDL and HDL particle subclass features in families with high cardiovascular risk and the presence of CAD and 2) to identify quantitative trait loci (QTLs) influencing the lipoprotein subfraction patterns, which we assessed by genome-wide linkage analysis
Summary
The HDL and LDL subclass profile is an emerging cardiovascular risk factor. Yet, the biological and genetic mechanisms controlling the lipoprotein subclass distribution are unclear. LDL and HDL cholesterol levels have been established as important risk factors for CAD, and the decrease of LDL cholesterol is a principal target in cardiovascular preventive strategies [1] It has been known for several years that the major lipoprotein classes can be further characterized into subfractions. The cholesterol content per particle exhibits large interindividual variation It is unclear which biological mechanisms control the lipoprotein subclass distribution. We aimed 1) to determine the heritability of the entire spectrum of LDL and HDL particle subclass features in families with high cardiovascular risk and the presence of CAD and 2) to identify quantitative trait loci (QTLs) influencing the lipoprotein subfraction patterns, which we assessed by genome-wide linkage analysis. Fischer contributed to this work. 2 To whom correspondence should be addressed
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