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Physiol. Genomics (January 13, 2004). doi:10.1152/physiolgenomics.00124.2003
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Submitted on July 25, 2003
Accepted on December 24, 2003

Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain

Carrie L Welch1*, Sara Bretschger2, Ping-Zi Wen3, Margarete Mehrabian3, Nashat Latib1, Jamila Fruchart-Najib4, Jean Charles Fruchart4, Christy Myrick5, and Aldons J Lusis6

1 Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY, USA
2 Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY, USA; Institute of Human Nutrition, Columbia University, New York, NY, USA
3 Department of Medicine, University of California, Los Angeles, CA, USA
4 Department of Atherosclerosis, Pasteur Institute, Lille, France
5 University of Florida, Gainesville, FL, USA
6 Department of Medicine, University of California, Los Angeles, CA, USA; Microbiology and Molecular Genetics, University of California, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA

* To whom correspondence should be addressed. E-mail: cbw13{at}columbia.edu.

Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identified Apoa2 as a major determinant of high density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level QTLs, while controlling for the effect of the Apoa2 locus, we performed linkage analysis in 179 chow-fed F2 mice derived from strains BALB/cJ and B6.C-H25c (a congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs, and one suggestive locus, were identified. A female-specific locus mapping to chromosome 6 also exhibited effects on plasma non-HDL-C, apolipoprotein (apo) AII, apo B, and apo E levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6: p=0.003 and p=0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.




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