Quantitative trait locus analysis of circulating adhesion molecules in hyperlipidemic apolipoprotein E-deficient mice.
Quantitative trait locus analysis of circulating adhesion molecules in hyperlipidemic apolipoprotein E-deficient mice.
复制标题
高脂血症载脂蛋白 E 缺陷小鼠循环粘附分子的定量性状位点分析。
DOI：
10.1007/s00438-008-0371-0
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Shi,Weibin
中科院分区：
文献类型：
--
作者：
Yuan,Zuobiao;Su,Zhiguang;Miyoshi,Toru;Rowlan,JessicaS;Shi,Weibin
循环可溶性粘附分子已被认为是预测动脉粥样硬化、2型糖尿病、肥胖和高血压等临床疾病的有用标志物。为了确定影响血浆可溶性血管细胞粘附分子-1（VCAM-1）和P-选择素水平的遗传因素，对载脂蛋白E-缺陷（apoE-/-）的C57 BL/6 J（B6）和C3 H/HeJ（C3 H）小鼠品系之间的互交进行了数量性状位点（QTL）分析。雌性F2小鼠饲喂西方饮食12周。在第9染色体上发现了一个显著影响可溶性VCAM-1水平的QTL，命名为Vcam 1（71 cM，LOD 3.9），在第5、13和15染色体上发现了3个暗示性QTL。可溶性P-选择素水平控制一个显着的QTL，命名为selp 1（8.5 cM，LOD 3.4），在第16号染色体和两个暗示QTL上的第10和13号染色体。在F2人群中，两种粘附分子均表现出与体重、总胆固醇和LDL/VLDL胆固醇水平显著或明显的相关趋势。这些结果表明，血浆VCAM-1和P-选择素水平是由多个基因调控的复杂性状，这种调控至少部分是通过作用于高脂血症apoE−/−小鼠的体重和脂质代谢来实现的。
Circulating soluble adhesion molecules have been suggested as useful markers to predict several clinical conditions such as atherosclerosis, type 2 diabetes, obesity, and hypertension. To determine genetic factors influencing plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, quantitative trait locus (QTL) analysis was performed on an intercross between C57BL/6J (B6) and C3H/HeJ (C3H) mouse strains deficient in apolipoprotein E-deficient (apoE−/−). Female F2mice were fed a western diet for 12 weeks. One significant QTL, namedsVcam1(71 cM, LOD 3.9), on chromosome 9 and three suggestive QTLs on chromosomes 5, 13 and 15 were identified to affect soluble VCAM-1 levels. Soluble P-selectin levels were controlled by one significant QTL, namedsSelp1(8.5 cM, LOD 3.4), on chromosome 16 and two suggestive QTLs on chromosomes 10 and 13. Both adhesion molecules showed significant or an apparent trend of correlations with body weight, total cholesterol, and LDL/VLDL cholesterol levels in the F2population. These results indicate that plasma VCAM-1 and P-selectin levels are complex traits regulated by multiple genes, and this regulation is conferred, at least partially, by acting on body weight and lipid metabolism in hyperlipidemic apoE−/−mice.