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Quantitative trait locus analysis of circulating adhesion molecules in hyperlipidemic apolipoprotein E-deficient mice

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Abstract

Circulating soluble adhesion molecules have been suggested as useful markers to predict several clinical conditions such as atherosclerosis, type 2 diabetes, obesity, and hypertension. To determine genetic factors influencing plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, quantitative trait locus (QTL) analysis was performed on an intercross between C57BL/6J (B6) and C3H/HeJ (C3H) mouse strains deficient in apolipoprotein E-deficient (apoE−/−). Female F2 mice were fed a western diet for 12 weeks. One significant QTL, named sVcam1 (71 cM, LOD 3.9), on chromosome 9 and three suggestive QTLs on chromosomes 5, 13 and 15 were identified to affect soluble VCAM-1 levels. Soluble P-selectin levels were controlled by one significant QTL, named sSelp1 (8.5 cM, LOD 3.4), on chromosome 16 and two suggestive QTLs on chromosomes 10 and 13. Both adhesion molecules showed significant or an apparent trend of correlations with body weight, total cholesterol, and LDL/VLDL cholesterol levels in the F2 population. These results indicate that plasma VCAM-1 and P-selectin levels are complex traits regulated by multiple genes, and this regulation is conferred, at least partially, by acting on body weight and lipid metabolism in hyperlipidemic apoE−/− mice.

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Acknowledgments

The current study was supported by the National Institutes of Health grant HL75433 and by the NHLBI Mammalian Genotyping Service (contract HV48141) for the genotyping.

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Authors and Affiliations

  1. Department of Radiology, University of Virginia, MR4 Room 1171, 409 Lane Road, Box 801339, Charlottesville, VA, 22908, USA

    Zuobiao Yuan, Zhiguang Su, Toru Miyoshi, Jessica S. Rowlan & Weibin Shi

  2. Department of Biochemistry and Molecular Genetics, University of Virginia, MR4 Room 1171, 409 Lane Road, Box 801339, Charlottesville, VA, 22908, USA

    Zuobiao Yuan, Zhiguang Su, Toru Miyoshi, Jessica S. Rowlan & Weibin Shi

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  1. Zuobiao Yuan
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  2. Zhiguang Su
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  3. Toru Miyoshi
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  5. Weibin Shi
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Correspondence to Weibin Shi.

Additional information

Communicated by P. Ruiz.

Zuobiao Yuan and Zhiguang Su contributed equally.

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Yuan, Z., Su, Z., Miyoshi, T. et al. Quantitative trait locus analysis of circulating adhesion molecules in hyperlipidemic apolipoprotein E-deficient mice. Mol Genet Genomics 280, 375–383 (2008). https://doi.org/10.1007/s00438-008-0371-0

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  • DOI: https://doi.org/10.1007/s00438-008-0371-0

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