Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA.
Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
Genes (Basel). 2022 Mar 14;13(3):510. doi: 10.3390/genes13030510.
Type 2 diabetes (T2D) is a major risk for atherosclerosis and its complications. -null () mouse strains exhibit a wide range of variations in susceptibility to T2D and carotid atherosclerosis, with the latter being a major cause of ischemic stroke. To identify genetic connections between T2D and carotid atherosclerosis, 145 male F2 mice were generated from LP/J and BALB/cJ mice and fed 12 weeks of a Western diet. Atherosclerotic lesions in the carotid arteries, fasting, and non-fasting plasma glucose levels were measured, and genotyping was performed using miniMUGA arrays. Two significant QTL (quantitative trait loci) on chromosomes (Chr) 6 and 15 were identified for carotid lesions. The Chr15 QTL coincided precisely with QTL for fasting and non-fasting glucose levels. Carotid lesion sizes showed a trend toward correlation with fasting and non-fasting glucose levels in F2 mice. The Chr15 QTL for carotid lesions was suppressed after excluding the influence from fasting or non-fasting glucose. Likely candidate genes for the causal association were , , and . These results demonstrate a causative role for hyperglycemia in the development of carotid atherosclerosis in hyperlipidemic mice.
2 型糖尿病（T2D）是动脉粥样硬化及其并发症的主要危险因素。-null() 小鼠品系表现出对 T2D 和颈动脉粥样硬化易感性的广泛差异，后者是缺血性中风的主要原因。为了确定 T2D 和颈动脉粥样硬化之间的遗传联系，从 LP/J 和 BALB/cJ 小鼠中产生了 145 只雄性 F2 小鼠，并喂食 12 周的西方饮食。测量了颈动脉粥样硬化病变、空腹和非空腹血糖水平，并使用 miniMUGA 阵列进行了基因分型。在第 6 和 15 号染色体上鉴定出两个与颈动脉病变相关的显著 QTL（数量性状位点）。Chr15 QTL 与空腹和非空腹血糖水平的 QTL 完全吻合。在 F2 小鼠中，颈动脉病变的大小与空腹和非空腹血糖水平呈趋势相关。排除空腹或非空腹血糖的影响后，Chr15 颈动脉病变 QTL 受到抑制。可能的候选基因是、和。这些结果表明，高血糖在高脂血症小鼠颈动脉粥样硬化的发展中起因果作用。
