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Journal of Lipid Research, Vol. 46, 2289-2294, October 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats

Makoto Asahina, Masao Sato and Katsumi Imaizumi¹

Laboratory of Nutrition Chemistry, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan

Published, JLR Papers in Press, August 1, 2005. DOI 10.1194/jlr.M500257-JLR200

¹ To whom correspondence should be addressed. e-mail: imaizumi{at}agr.kyushu-u.ac.jp

The exogenously hypercholesterolemic (ExHC) rat is an established strain that exhibits a polygenic syndrome of hypercholesterolemia after feeding on a cholesterol-containing diet, and the extent of this differs between male and female rats in the strain. The present study was performed to determine the genetic background of diet-induced hypercholesterolemia in ExHC rats. We used quantitative trait locus (QTL) analyses of the F2 progeny derived from ExHC and Brown-Norway rats. Rats were fed a diet containing 1% cholesterol, and a genome-wide scan was then performed. Significant QTLs for serum total cholesterol levels were revealed on chromosomes 5 and 14 in the vicinity of markers D5Rat95 and D14Rat43, having maximum logarithm of the odds scores of 6.0 and 5.8, respectively. A suggestive QTL for the trait was also detected on chromosome 3 at D3Rat140. In particular, the QTL on chromosome 5 was specific for female rats. These loci were novel QTLs for postdietary serum total cholesterol levels. In addition, cross-mating analysis in F1 generations suggested that the responsiveness to dietary cholesterol in ExHC rats is partly attributable to X-linked inheritance.

Identifying such genetic factors may be useful in predicting the risks associated with diet-induced hypercholesterolemia in humans.

Abbreviations: BN, Brown-Norway; cM, centimorgan; ExHC, exogenously hypercholesterolemic; LOD, logarithm of the odds; LRS, likelihood ratio statistic; QTL, quantitative trait locus; SD, Sprague-Dawley; WAT, white adipose tissue

Supplementary key words dietary cholesterol • quantitative trait locus • serum cholesterol • sex difference • X-linked inheritance

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