Katano Hiroyuki, Nishikawa Yusuke, Yamada Hiroshi, Iwata Takashi, Mase Mitsuhito
Department of Neurosurgery and Medical Informatics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Department of Neurosurgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Surg Neurol Int. 2020 Sep 12;11:286. doi: 10.25259/SNI_387_2020. eCollection 2020.
The precise mechanisms of carotid calcification and its clinical significance have not been established.
We classified ten plaques from carotid endarterectomy patients into high- and low-calcified plaques based on the Agatston calcium scores. We performed whole-exome sequencing for genetic profiles with single nucleotide variations (SNVs), insertions, and deletions. Bioinformatic data mining was then conducted to disclose specific gene variations to either high- or low-calcified carotid plaques.
In the carotid plaques, G:C>A:T/C:G>T:A transitions as SNVs, insT after C/insC after A as insertions, and delA after G/delT after C as deletions were most frequently observed, but no significant difference was observed between the high- and low-calcified plaque groups in their proportion of base-pair substitution types. In the bioinformatic analysis, SNVs of ATP binding cassette subfamily C member 6 () were more commonly found in high-calcified plaques and SNVs of were more commonly found in low-calcified plaques compared to the other group. No new genetic variants related to calcification or atherosclerosis among those not registered in dbSNP was detected.
Our findings clarified the features of base-pair substitutions in carotid plaques, showing no relation to calcification. However, genetic variants in relating to vascular calcification for high-calcified plaques, and in encoding kallikrein associated with vascular regulation of atherosclerosis for low-calcified plaques were more specifically extracted. These results contribute to a better understanding of the genetic basis of molecular activity and calcium formation in carotid plaques.
颈动脉钙化的确切机制及其临床意义尚未明确。
我们根据阿加斯顿钙评分，将接受颈动脉内膜切除术患者的10个斑块分为高钙化斑块和低钙化斑块。我们对具有单核苷酸变异（SNV）、插入和缺失的基因谱进行了全外显子组测序。然后进行生物信息学数据挖掘，以揭示高钙化或低钙化颈动脉斑块的特定基因变异。
在颈动脉斑块中，最常观察到的是作为SNV的G:C>A:T/C:G>T:A转换、作为插入的C后insT/A后insC以及作为缺失的G后delA/C后delT，但高钙化斑块组和低钙化斑块组在碱基对替代类型比例上未观察到显著差异。在生物信息学分析中，与另一组相比，ATP结合盒亚家族C成员6（）的SNV在高钙化斑块中更常见，而的SNV在低钙化斑块中更常见。在dbSNP中未注册的那些基因中，未检测到与钙化或动脉粥样硬化相关的新基因变异。
我们的研究结果阐明了颈动脉斑块中碱基对替代的特征，表明与钙化无关。然而，更具体地提取了与高钙化斑块血管钙化相关的基因变异，以及与低钙化斑块动脉粥样硬化血管调节相关的激肽释放酶编码基因变异。这些结果有助于更好地理解颈动脉斑块中分子活性和钙形成的遗传基础。
