Genetic analysis of atherosclerosis and glucose homeostasis in an intercross between C57BL/6 and BALB/cJ apolipoprotein E-deficient mice.
Genetic analysis of atherosclerosis and glucose homeostasis in an intercross between C57BL/6 and BALB/cJ apolipoprotein E-deficient mice.
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C57BL/6 和 BALB/cJ 载脂蛋白 E 缺陷小鼠杂交后动脉粥样硬化和葡萄糖稳态的遗传分析。
DOI：
10.1161/circgenetics.111.961649
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Shi,Weibin
中科院分区：
文献类型：
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作者：
Zhang,Zhimin;Rowlan,JessicaS;Wang,Qian;Shi,Weibin
背景与非糖尿病个体相比，糖尿病患者发生动脉粥样硬化及相关并发症的风险增加。与糖尿病相关的心血管风险增加部分是由于影响葡萄糖稳态和动脉粥样硬化病变生长的遗传变异。当缺乏载脂蛋白E（Apoe−/−）时，小鼠品系C57 BL/6 J（B6）和BALB/cJ（BALB）在空腹血糖和动脉粥样硬化病变大小方面表现出明显差异。进行数量性状位点（QTL）分析，以确定遗传因素影响的2 phenotypes.Methods和ResultsF 2雌性小鼠（n=266）之间的互交B6. Apoe −/−和BALB.Apoe−/−小鼠和西方饮食喂养12周。测量主动脉根部的动脉粥样硬化病变、空腹血糖和体重。对整个基因组的130个微卫星标记进行了基因分型。在第1、2、5、9号染色体上分别检测到4个与动脉粥样硬化斑块大小相关的QTL，分别为Ath 1、Ath 41、Ath 42、Ath 29，在第4号染色体上检测到1个与动脉粥样硬化斑块大小相关的QTL。结果表明，在普通饲料中，有4个QTL对空腹血糖水平有显著影响，分别位于第1、第5、第12、第9和第15染色体上，分别为Bglu 3和Bglu 12，Bglu 13和Bglu 15。在西式饮食的空腹血糖中发现了两个显着的QTL Bglu 3和Bglu 13，以及Chr 8上的1个提示位点。在Chr 1上发现了一个显著性位点，在Chr 9和Chr 19上发现了2个提示性位点，分别与Bglu 3和Bglu 13在置信区间内一致。动脉粥样硬化和糖尿病的QTL共定位表明这两种疾病之间可能存在遗传联系。
BackgroundDiabetic patients have an increased risk of developing atherosclerosis and related complications compared with nondiabetic individuals. The increased cardiovascular risk associated with diabetes is due in part to genetic variations that influence both glucose homeostasis and atherosclerotic lesion growth. Mouse strains C57BL/6J (B6) and BALB/cJ (BALB) exhibit distinct differences in fasting plasma glucose and atherosclerotic lesion size when deficient in apolipoprotein E (Apoe−/−). Quantitative trait locus (QTL) analysis was performed to determine genetic factors influencing the 2 phenotypes.Methods and ResultsFemale F2mice (n=266) were generated from an intercross between B6.Apoe−/−and BALB.Apoe−/−mice and fed a Western diet for 12 weeks. Atherosclerotic lesions in the aortic root, fasting plasma glucose, and body weight were measured. 130 microsatellite markers across the entire genome were genotyped. Four significant QTLs,Ath1on chromosome (Chr) 1,Ath41on Chr2,Ath42on Chr5, andAth29on Chr9, and 1 suggestive QTL on Chr4, were identified for atherosclerotic lesion size. Four significant QTLs,Bglu3andBglu12on Chr1,Bglu13on Chr5,Bglu15on Chr12, and 2 suggestive QTLs on Chr9 and Chr15 were identified for fasting glucose levels on the chow diet. Two significant QTLs,Bglu3andBglu13, and 1 suggestive locus on Chr8 were identified for fasting glucose on the Western diet. One significant locus on Chr1 and 2 suggestive loci on Chr9 and Chr19 were identified for body weight.Ath1andAth42coincided withBglu3andBglu13, respectively, in the confidence interval.ConclusionsWe have identified novel QTLs that have major influences on atherosclerotic lesion size and glucose homeostasis. The colocalization of QTLs for atherosclerosis and diabetes suggests possible genetic connections between the 2 diseases.