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Int J Mol Epidemiol Genet 2012;3(2):174-178

Original Article
Hemodynamic fluid shear stress response genes and carotid intima-media
thickness: a candidate gene association analysis in the cardiovascular health

Astrid M Suchy-Dicey, Daniel A Enquobahrie, Susan R Heckbert, Jerome I Rotter, Bruce M Psaty, Barbara McKnight

Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101 USA; Cedars-Sinai Medical Center
8700 Beverly Boulevard, Los Angeles, CA 90048 USA; Department of Epidemiology, School of Public Health, University of
Washington, Seattle, WA; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA;
Department of Medicine, School of Medicine, University of Washington, Seattle, WA

Received May 2, 2012; accepted May 17, 2012; Epub May 21, 2012; Published May 30, 2012

Abatract: Objective: This study examined whether carotid artery intimal-medial thickness (cIMT) is associated with genetic
variations (SNPs) in a hemodynamics-responsive gene pathway. Methods: Subjects were Cardiovascular Health Study
participants free of cardiovascular events at baseline (N=3388). Genotype was measured using Illumina 370CNV HumanHap
chip. Carotid IMT was measured using ultrasound. Estimated mean differences in cIMT per additional minor allele for 366
SNPs in MAP2K5, MAPK7, MEF2A/C, and KLF2 were adjusted for sex, age, clinic, and medication use. SNP-SNP interactions
were examined using logic regression for 71 tagSNPs. Results: None of the associations was significant after correction for
multiple comparisons; smallest P-value=0.065 for MAP2K5 and common cIMT. The best-performing logic regression tree
combined two SNPs in MAP2K5—rs745212 and rs12905175—and common cIMT; this association was not significant,
corrected P-value=0.062. Conclusion: There was not strong evidence of association between genetic variants in a
hemodynamics-responsive gene pathway and atherosclerosis among older adults. (IJMEG1204005).

Keywords: Cardiovascular Health Study (CHS), candidate gene study, carotid intima-media thickness (cIMT), hemodynamics
response, fluid shear stress, endothelium / endothelial cells, Kruppel-like factor 2 (KLF2), Mitogen-activated protein kinase 7
(MAPK7), Myocyte-specific enhancer factor 2 A/C (MEF2A/C), Mitogen-activated protein kinase kinase 5 (MAP2K5)

Address all correspondence to:
Dr. Daniel A Enquobahrie
1730 Minor Avenue, Suite 1360
Seattle WA 98101, USA.
Tel: 001-206-287-2390; Fax 001-206-287-2662
E-mail: danenq@u.washington.edu