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