Background/Purpose: In the general population individuals with coronary artery disease (CAD) have a significantly increased frequency of particular susceptibility single nucleotide polymorphisms (SNPs). Since CAD is increased in rheumatoid arthritis (RA), we sought to determine whether RA patients with CAD will have an increased frequency of these SNPs compared to those without CAD, implying that RA enhances the risk for CAD by acting on established genetic pathways predisposing to CAD, or alternatively, whether RA acts to increase CAD by mechanisms independent of these genetic pathways.

Methods: CAD was assessed by coronary artery calcification (CAC) using computed-tomography in 561 patients with RA. 100 SNPs associated with CAD in the general population were genotyped or imputed and their relation to CAC established through multiple regression analysis for individual SNPs and a genetic risk score (GRS) representing their cumulative effect.

Results: Ninety-one CAD SNPs were genotyped successfully; these were not significantly associated with CAC (Agatston units) or different CAC categorizations, either individually or collectively in the GRS. Only rs6544713 (ABCG8), rs3869109 (HCG27), rs1332844 (PHACTR1), rs579459 (ABO), rs4773144 (COL4A2), rs2075650 (TOMM40) and rs9982601 (KCNE2) expressed any positive relation with CAC in one or more of the analyses. Notably, none of the group of the 12 SNPs mapping in the 53 kb region of chromosome 9p21 that are among the strongest predictors of CAD in the general population exhibited any association with CAD. Moreover, rs1333040 (CDKN2B-AS1), which in the general population is positively associated with CAD risk, showed a significant inverse association between genotype and CAC. Only rs579459 (ABO) exhibited a consistent positive association between genotype and CAC score, with a significant increase of the effect allele frequency in both homozygous or heterozygous genotype distributions. When the association of the CAD related SNPS with CAC was studied through the non weighted and weighted set of SNPs, no significant association was found. In particular, an increase in the number of homozygous cardiovascular disease related SNPs was not significantly associated with an increase in logCAC Agatston units. GRS was not associated with CAC both in the univariate, and in the multivariate analysis adjusted for age and sex and for traditional cardiovascular factors. Additionally, when CAD related SNPs were weighted by their effect sizes, the resulting GRS was not significantly associated with CAC. Besides, trend analysis showed no relation between GRS and log CAC Agatson units (p=0.93). Interestingly, the positive association found between DAS28 and CAC after adjusting for traditional cardiovascular risk factors was not modified by correcting for the CAD related SNPs GRS.

Conclusion: The increased risk for CAC in RA does not appear to primarily operate through established genetically regulated atherogenic mechanisms that are preponderant in the general population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/coronary-artery-calcification-in-rheumatoid-arthritis-patients-is-not-characterized-by-an-increase-in-genes-associated-with-coronary-artery-disease-in-the-general-population/