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-con- taining 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 hyper- cholesterolemia in ExHC rats. We used quantitative trait lo- cus (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 re- vealed 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 fe- male rats. These loci were novel QTLs for postdietary se- rum total cholesterol levels. In addition, cross-mating analy- sis 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, M., M. Sato, and K. Imaizumi. Genetic analysis of diet-induced hyper- cholesterolemia in exogenously hypercholesterolemic rats. J. Lipid Res. 2005. 46: 2289-2294.