Abstract 3075: The Chromosome 9p21 Risk Variant rs10757278 is Associated with Increased Arterial Stiffness
Background: The chromosome 9p21 locus is associated with risk of CAD and MI. The mechanisms underlying this risk are poorly understood with the variant residing in a non-coding region. The same variant is also associated with intracranial aneurysms leading to suggestions that it may promote atherosclerosis by influencing the structure and function of the arterial wall. We hypothesized that subjects with the 9p21 risk allele will have abnormal arterial function reflected as greater arterial stiffness.
Methods: Subjects undergoing elective cardiac catheterization were enrolled as part of the Emory Cardiac Genebank and studied 2 hrs post procedure (n=74, mean age 63.6, 68% male). Arterial stiffness was measured using applanation tonometry (Sphygmocor©) with augmentation index corrected for heart rate (Aix75) and central augmented pressure (cAP75) as the outcome variables. The rs10757278 SNP was genotyped using a Centaurus platform (deCODE Genetics). We compared subjects using an additive model for the risk allele G; GG vs. AG/GA vs. AA (n=21, 34, 19 respectively).
Results: The genotype groups did not differ in terms of age, gender and common risk factors. We found a significant difference between the groups in Aix75 (p=0.026) and cAP75 (p=0.014), which remained significant after adjusting for age, gender, mean BP and CAD severity (p=0.043 and p=0.027, respectively) Figure⇓.
Conclusion: In conclusion, we found that the 9p21 variant rs10757278 is associated with increased arterial stiffness, suggesting that the mechanisms underlying the increased susceptibility to CAD and aneurysms with this variant may in part be due to alteration of arterial functional characteristics.