Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats.
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 post-dietary 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.
Asahina
Makoto
M
Laboratory of Nutrition Chemistry, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Sato
Masao
M
Imaizumi
Katsumi
K
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D003433:Crosses, Genetic; D005260:Female; D006937:Hypercholesterolemia / Q000235:genetics*; D008297:Male; D040641:Quantitative Trait Loci; D051381:Rats; D011914:Rats, Inbred BN; D012737:Sex Factors
D002791:Cholesterol, Dietary; D002784:Cholesterol