Profile of genetic variations in severely calcified carotid plaques by whole-exome sequencing.
Profile of genetic variations in severely calcified carotid plaques by whole-exome sequencing.
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DOI：
10.25259/sni_387_2020
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发表时间：
2020
影响因子：
--
通讯作者：
Mase M
中科院分区：
文献类型：
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作者：
Katano H;Nishikawa Y;Yamada H;Iwata T;Mase M
颈动脉钙化的确切机制及其临床意义尚不清楚。我们根据Agatston钙化评分将颈动脉内膜切除术患者的10块斑块分为高钙化斑块和低钙化斑块。我们对单核苷酸变异(SNV)、插入和缺失的基因图谱进行了完整的外显子组测序。然后进行生物信息数据挖掘，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，G：C>；A：T/C：G>；T：A转换为SNV，C/iNSC后插入Inst，C as缺失后G/delt后Dela最常见，但高钙化斑块组和低钙化斑块组之间碱基对替换类型的比例无显著差异。在生物信息学分析中，高钙化斑块中ATP结合盒C亚家族成员6(ADCC6)的SNV较多见，低钙化斑块中KLKB1的SNV较多见。在那些未在数据库SNP中注册的人中，没有检测到与钙化或动脉粥样硬化相关的新的遗传变异。我们的发现阐明了颈动脉斑块中碱基对替换的特征，显示与钙化无关。然而，ADCC6中与高钙化斑块的血管钙化有关的遗传变异，以及KLKB1中编码激肽释放酶与低钙化斑块的动脉粥样硬化的血管调节相关的基因变体被更具特异性地提取。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。
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 (ADCC6) were more commonly found in high-calcified plaques and SNVs of KLKB1 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 ADCC6 relating to vascular calcification for high-calcified plaques, and in KLKB1 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.