Profile of genetic variations in severely calcified carotid plaques by whole-exome sequencing

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.