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Int J Mol Epidemiol Genet 2013;4(4):258-267

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

Weihong Tang, Alanna Morrison, Bruce A Wasserman, Aaron R Folsom, Wei Sun, Stephen Campbell, W H Linda Kao, Eric
Boerwinkle

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA;
Human Genetics Center and Division of Epidemiology, University of Texas Health Science Center at Houston, Houston, TX,
USA; Department of Radiology, Johns Hopkins University, Baltimore, MD, USA; Department of Biostatistics, University of North
Carolina School of Public Health, Chapel Hill, NC, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of
Public Health, Baltimore, MD, USA; Human Genetics Center and Institute for Molecular Medicine, University of Texas Health
Science Center at Houston, Houston, TX, USA

Received October 28, 2013; Accepted November 12, 2013; Epub November 28, 2013; Published December 15, 2013

Abstract: 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. (IJMEG1310005).

Keywords: SERPINA9 gene, carotid atherosclerosis, MRI, genetic association

Address correspondence to: Dr. Weihong Tang, Division of Epidemiology and Community Health, School of Public Health,
University of Minnesota, 1300 South Second Street, WBOB 300, Minneapolis, MN 55454, USA. Tel: 612-626-9140; Fax:
612-624-0315; E-mail: tang0097@umn.edu