J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700338-JLR200 on December 28, 2007

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Journal of Lipid Research, Vol. 49, 715-723, April 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

The lipoprotein subfraction profile: heritability and identification of quantitative trait loci

Bernhard Kaess1,*, Marcus Fischer1,*, Andrea Baessler*, Klaus Stark*, Fritz Huber{dagger}, Werner Kremer{dagger}, Hans Robert Kalbitzer{dagger}, Heribert Schunkert§, Guenter Riegger* and Christian Hengstenberg2,*

* Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany
{dagger} Institut für Biophysik und Physikalische Biochemie, University of Regensburg, and Lipofit GmbH, Regensburg, Germany
§ Medizinische Klinik II, University Hospital of Schleswig-Holstein, Lübeck, Germany

Published, JLR Papers in Press, December 28, 2007.

1 B. Kaess and M. Fischer contributed equally to this work.

2 To whom correspondence should be addressed. e-mail: 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. 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.

Supplementary key words linkage analysis • HDL • LDL • subclasses • nmr spectroscopy


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