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


CONCLUSIONS
There was not strong evidence of association between genetic variants in a hemodynamics-responsive gene pathway and atherosclerosis among older adults.
Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101 USA.
Astrid M
AM
Suchy-Dicey
Daniel A
DA
Enquobahrie
Susan R
SR
Heckbert
Jerome I
JI
Rotter
Bruce M
BM
Psaty
Barbara
B
McKnight