Quantitative trait locus analysis of circulating adhesion molecules in hyperlipidemic apolipoprotein E-deficient mice.
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.
Yuan
Zuobiao
Z
Department of Radiology, University of Virginia, MR4 Room 1171, 409 Lane Road, Box 801339, Charlottesville, VA 22908, USA.
Su
Zhiguang
Z
Miyoshi
Toru
T
Rowlan
Jessica S
JS
Shi
Weibin
W
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D001835:Body Weight; D008076:Cholesterol, HDL / Q000097:blood; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D006949:Hyperlipidemias / Q000097:blood* / Q000209:etiology / Q000473:pathology; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics; D008810:Mice, Inbred C57BL / Q000235:genetics; D018345:Mice, Knockout; D019007:P-Selectin / Q000097:blood* / Q000235:genetics; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D019007:P-Selectin; D014280:Triglycerides; D019010:Vascular Cell Adhesion Molecule-1