Abstract 2324: The Lipoprotein Subfraction Profile: Heritability and Identification of Quantitative Trait Loci
LDL and HDL cholesterol are routine parameters in assessing cardiovascular risk. However, over the last years there has been growing evidence that distinct lipoprotein particle features, i.e. particle concentration, mean size and subclass distribution, provide much more prognostic information than the assessment of their cholesterol content. Yet, the biological and genetic mechanisms controlling the lipoprotein subclass distribution are unclear. Therefore, we aimed  to determine the heritability of the entire spectrum of LDL and HDL subclass features in siblings and  to identify gene loci influencing the lipoprotein subfraction pattern.
Methods: We used NMR spectroscopy to analyze the lipoprotein subclass distribution in 1.275 CAD patients derived from the Regensburg myocardial infarction family study. We calculated heritability estimates, performed a microsatellite genome scan and calculated linkage for all subfractions.
Results: HDL and LDL subclass profiles showed heritabilities ranging from 31–67% (all p<10–5) for HDL and 23–48% (all p<10–3) for LDL traits using univariate calculation. After multivariate adjustment, we found heritability estimates of 27–48% (all p<0.05) and 21–44%, respectively. The linkage scan revealed a significant LOD score of 3.3 for HDL particle concentration on chromosome 18 as well as a highly suggestive signal for HDL size on chromosome 12 (2.9). After multivariate adjustment, we found a maximum LOD score of 3.7 for HDL size.
Conclusion: 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 and may allow the development of new therapeutic strategies.