New quantitative trait loci for carotid atherosclerosis identified in an intercross derived from apolipoprotein E-deficient mouse strains.

New quantitative trait loci for carotid atherosclerosis identified in an intercross derived from apolipoprotein E-deficient mouse strains.
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DOI:
10.1152/physiolgenomics.00099.2012
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发表时间:
2013-04-16
影响因子:
4.6
通讯作者:
Shi W
Shi W
中科院分区:
生物学3区
文献类型:
--
作者:
Rowlan JS;Zhang Z;Wang Q;Fang Y;Shi W

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颈动脉粥样硬化是缺血性卒中的主要原因。为了确定导致颈动脉粥样硬化的遗传因素,我们使用来自C57 BL/6 J(B6)和BALB/cJ(BALB)载脂蛋白E(Apoe−/−)小鼠间杂交的雌性小鼠进行了数量性状位点(QTL)分析。我们在6周龄时开始对266只F2小鼠进行西方饮食,并将它们喂食饮食12周。测量左颈动脉分叉处的动脉粥样硬化病变和血脂水平。我们对整个基因组的130个微卫星标记进行了基因分型。在第12号染色体(Chr)上检测到3个显著性QTL,即Cath 1、Cath 2和Cath 3,在第6、9、17和18号染色体上检测到4个提示性QTL。Chr 6基因座复制了一个暗示性QTL,并命名为Cath 4。共检测到6个HDL、3个non-HDL胆固醇和3个甘油三酯的QTL,其中在Chr 1上的60.3cM处检测到一个non-HDL的QTL,命名为Nhdl 13,在ChrX上检测到一个HDL的QTL。HDL(Hdlq 5)的一个重要位点与Chr 9颈动脉病变的提示位点重叠。在F2人群中观察到颈动脉病变大小与HDL胆固醇水平之间存在显著相关性(R =-0.153,P = 0.0133)。因此,我们已经确定了几个新的颈动脉粥样硬化的QTL和Chr 9上的位点可能通过与HDL的相互作用发挥作用。
Carotid atherosclerosis is the primary cause of ischemic stroke. To identify genetic factors contributing to carotid atherosclerosis, we performed quantitative trait locus (QTL) analysis using female mice derived from an intercross between C57BL/6J (B6) and BALB/cJ (BALB) apolipoprotein E (Apoe−/−) mice. We started 266 F2 mice on a Western diet at 6 wk of age and fed them the diet for 12 wk. Atherosclerotic lesions in the left carotid bifurcation and plasma lipid levels were measured. We genotyped 130 microsatellite markers across the entire genome. Three significant QTLs, Cath1 on chromosome (Chr) 12, Cath2 on Chr5, and Cath3 on Chr13, and four suggestive QTLs on Chr6, Chr9, Chr17, and Chr18 were identified for carotid lesions. The Chr6 locus replicated a suggestive QTL and was named Cath4. Six QTLs for HDL, three QTLs for non-HDL cholesterol, and three QTLs for triglyceride were found. Of these, a significant QTL for non-HDL on Chr1 at 60.3 cM, named Nhdl13, and a suggestive QTL for HDL on ChrX were new. A significant locus for HDL (Hdlq5) was overlapping with a suggestive locus for carotid lesions on Chr9. A significant correlation between carotid lesion sizes and HDL cholesterol levels was observed in the F2 population (R = −0.153, P = 0.0133). Thus, we have identified several new QTLs for carotid atherosclerosis and the locus on Chr9 may exert effect through interactions with HDL.
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