{"id":"0a1f40b9-291b-49b7-8956-646da2c83bec","slug":"profile-of-genetic-variations-in-severely-calcified-carotid-plaques-by-whole-exome-sequencing","title":"Profile of genetic variations in severely calcified carotid plaques by whole-exome sequencing","authors":["Hiroyuki Katano","Yusuke Nishikawa","Hiroshi Yamada","Takashi Iwata","Mitsuhito Mase"],"abstract":"Background: The precise mechanisms of carotid calcification and its clinical significance have not been established. Methods: 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. Results: 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. Conclusion: 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.","thumbnailUrl":"https://sni-digital-videos.s3.amazonaws.com/articles/0a1f40b9-291b-49b7-8956-646da2c83bec/featured/hero-1781563160659.png","publishDate":"2020-09-12T00:00:00.000Z","doi":"10.25259/SNI_387_2020","categories":["Neurovascular","Original Article"],"fullTextUrl":"https://surgicalneurologyint.com/wp-content/uploads/2020/09/10254/SNI-11-286.pdf"}