Shared and Discrepant Susceptibility for Carotid Artery and Aortic Arch Calcification: A Genetic Association Study

Genome-wide association studies (GWASs) have identified several risk loci for coronary artery calcification. Four single-nucleotide polymorphisms (SNPs, rs1537370, rs1333049, rs2026458 and rs9349379) were associated with coronary artery calcification with P values less than 5 × 10(-8) in GWASs. It is unclear if these associations exist in other vascular beds. Thus, we evaluated the impacts of these four SNPs on carotid artery and aortic arch calcification in this study. Computed tomography was applied to quantify the calcification of carotid artery and aortic arch. 860 patients with stroke completed calcification quantification and genotype testing were included in data analysis. Each SNP was evaluated for the association with carotid artery calcification, and with aortic arch calcification using generalized linear model. Among the four tested SNPs, rs2026458 was associated with calcification in both carotid artery (β = 0.31, 95% confidence interval [CI] 0.10-0.52, P = 0.003) and aortic arch (β = 0.32, 95% CI 0.10-0.54, P = 0.004), while rs1333049 was only associated with carotid artery calcification (β = 0.28, 95% CI 0.06-0.50, P = 0.011). In gender-stratified analyses, rs2026458 had significant impacts on carotid artery (P = 0.003) and aortic arch calcification (P = 0.008) in male, but not in female patients; while rs1537370 was significantly associated with carotid artery calcification in female (P = 0.013), but not in male patients. In conclusion, SNPs associated with coronary artery calcification may also increase the risk of calcification in other arteries such as carotid artery and aortic arch.