Asahina Makoto, Sato Masao, Imaizumi Katsumi
Laboratory of Nutrition Chemistry, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
J Lipid Res. 2005 Oct;46(10):2289-94. doi: 10.1194/jlr.M500257-JLR200. Epub 2005 Aug 1.
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.
外源性高胆固醇血症（ExHC）大鼠是一个已确立的品系，在喂食含胆固醇饮食后会出现高胆固醇血症的多基因综合征，且该品系中雄性和雌性大鼠的这种情况存在差异。本研究旨在确定ExHC大鼠饮食诱导的高胆固醇血症的遗传背景。我们对ExHC大鼠和棕色挪威大鼠杂交产生的F2后代进行了数量性状基因座（QTL）分析。给大鼠喂食含1%胆固醇的饮食，然后进行全基因组扫描。在标记D5Rat95和D14Rat43附近的第5号和第14号染色体上发现了血清总胆固醇水平的显著QTL，其最大优势对数得分分别为6.0和5.8。在第3号染色体上的D3Rat140处也检测到了该性状的一个提示性QTL。特别是，第5号染色体上的QTL对雌性大鼠具有特异性。这些基因座是饮食后血清总胆固醇水平的新QTL。此外，F1代的杂交分析表明，ExHC大鼠对饮食胆固醇的反应性部分归因于X连锁遗传。确定此类遗传因素可能有助于预测人类饮食诱导的高胆固醇血症相关风险。
