Submitted on July 25, 2007
Revised on November 7, 2007
Accepted on December 28, 2007
The lipoprotein subfraction profile: heritability and identification of quantitative trait loci
Bernhard Kaess, Marcus Fischer, Andrea Baessler, Klaus Stark, Fritz Huber, Werner Kremer, Hans Robert Kalbitzer, Heribert Schunkert, Guenter Riegger, and Christian Hengstenberg
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg 93042
Corresponding Author: christian.hengstenberg{at}klinik.uni-regensburg.de
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. Objective: 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. Methods: Using NMR spectroscopy we analyzed the lipoprotein subclass distribution in 1.275 CAD patients derived from the Regensburg myocardial infarction family study. We calculated heritabilities, performed a microsatellite genome scan and calculated linkage. Results: HDL and LDL subclass profiles showed heritabilities ranging from 23-67% (all p<10-3) 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 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. Conclusions: 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.
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