Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats

Journal of Lipid Research

Makoto Asahina¹  Masao Sato¹  Katsumi Imaizumi² 

[1] Laboratory of Nutrition Chemistry, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan;To whom correspondence should be addressed.;

关键词: dietary cholesterol;    quantitative trait locus;    serum cholesterol;    sex difference;    X-linked inheritance;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown