Association of SERPINA9 gene variants with carotid artery atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study

The SNP rs11628722 in the SERPINA9 gene was previously associated with incident ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. Centerin, the protein encoded by SERPINA9, is involved in maturation and maintenance of naïve B cells, which play a role in atherogenesis. We investigated whether 21 tag SNPs in the SERPINA9 gene are associated with features of carotid artery atherosclerotic plaque measured by magnetic resonance imaging (MRI). Carotid MRI data were obtained from 1,282 European Americans and 341 African Americans of the ARIC Carotid MRI study, which recruited participants from ARIC by a stratified sampling plan that over-sampled participants with carotid intima-media thickening. Five MRI measures, focused on carotid wall volume, wall thickness, and lipid core, were analyzed. Genetic associations between the MRI measurements and each of the 21 SNPs were analyzed in linear regression models with adjustment for sample weights and traditional risk factors. Rs11628722 was tested a priori. In African Americans, rs11628722 was significantly associated with carotid wall volume (p < 0.05). Among the other 20 SNPs, adjusted for multiple testing, rs4905204, which encodes an Ala to Val amino acid change, was significantly associated with maximum wall thickness (p < 0.000625) and suggestively associated with total wall volume (p < 0.0026) in European Americans. In conclusion, SNPs in the SERPINA9 gene showed race-specific associations with characteristics of carotid atherosclerotic plaques. Replications in other populations are needed to validate findings of this study and to establish the SERPINA9 gene as a candidate in the etiology of carotid atherosclerosis.