Abstract 17183: Genetic Variants Primarily Associated with Rheumatoid Arthritis (RA) Do Not Effect Coronary Artery Disease Risk
Inflammatory conditions like rheumatoid arthritis (RA) have been suspected to affect the risk of coronary artery disease (CAD). Specifically, RA has been shown repeatedly to increase the risk of CAD. Recently, multiple single nucleotide polymorphisms (SNPs) have been identified to affect RA risk. If genetic mechanisms of this inflammatory disease and CAD are overlapping, one might expect that risk alleles for RA also increase the risk of CAD. As positive control for our genetically based approach, we studied LDL associated SNPs in identical fashion. We tested 20 SNPs that previously have been associated with RA at genome-wide significance (p<5x10-8) for association with CAD. We performed our analyses in CARDIoGRAM, a meta-analytical dataset including genome-wide association data from 22,233 CAD cases and 64,762 controls. Exactly half of RA risk alleles (n=10) displayed a directionality consistent positive association with CAD (OR range 1.0-1.04), whereas the other half of RA risk alleles (n=10) displayed an OR below 1 (range 0.93-0.99). Thus, this distribution is not different from that expected by chance (p=1). Two SNPs displayed p-values for CAD below the 5 percent level, these were rs26232 close to C5orf30 (OR 1.03, P=0.02) and rs6679677 close to PTPN22 (OR 0.93, P=0.001), again with directionalty inconsistent effect. By contrast, out of 24 LDL associated risk alleles, 18 displayed an odds ratio for CAD> 1 (p=0.03) and 11 LDL-SNPs produced p-values <0.05 with directionalty consistent effects on CAD risk. We found no evidence that RA-associated SNPs are also associated with CAD, suggesting different pathological mechanisms leading to RA and coronary atherosclerosis. Shared non-genetic factors may more plausibly explain the observed correlation of the two disease conditions RA and CAD.
- © 2012 by American Heart Association, Inc.