Study about genetic background of diet-induced hypercholesterolemia

饮食性高胆固醇血症遗传背景研究

• 批准号: 16580103
• 负责人: SATO Masao
• 金额: $ 2.5万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16580103/
• 关键词: QTL; ExHC rats; diet-induced hypercholesterolemia; コレステロール; 高コレステロール血症; コンジェニック系統

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.

外源性高胆固醇（ENGC）大鼠是一种已建立的菌株，在含胆固醇的饮食进食后表现出多基因胆固醇血症的多基因综合征，并且菌株中雄性大鼠之间的程度不同。进行本研究以确定exc大鼠饮食诱导的高胆固醇血症的遗传背景。我们使用了源自ENEMC和Brown-Norway大鼠的F2后代的定量性状基因座（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。在标记物D5RAT95和D14RAT43附近染色体5和14上揭示了血清总胆固醇水平的显着QTL，分别具有6.0和5.8的几率评分的最大对数。在D3RAT140处的3染色体上也检测到了该性状的暗示性QTL。特别是，5号染色体上的QTL特异于雌性大鼠。这些基因座是后血清总胆固醇水平的新型QTL。此外，F1代的交叉分析表明，ENEVC大鼠对饮食胆固醇的反应性部分归因于X连锁的遗传。识别这种遗传因素可能有助于预测与人类饮食诱导的高胆固醇血症相关的风险。

项目成果

Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic

外源性高胆固醇血症饮食诱发高胆固醇血症的遗传分析

• 发表时间: 2005
• 期刊: Journal of Lipid Research 46
• 作者: M.Asahina;M.Sato;K.Imaizumi
• 通讯作者: K.Imaizumi