Session Title: Genetics, Genomics and Proteomics
Session Type: Abstract Submissions (ACR)
Cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Traditional as well as disease related risk factors seem to contribute to the development.
To evaluate the impact of genetic makers for development of myocardial infarction (MI) or angina pectoris (AP) leading to coronary intervention (PTCA or CGBP) in patients with early RA in relation to inflammation and traditional risk factors.
Patients with early RA (1987 American College of Rheumatology criteria) from northern Sweden and consecutively recruited since Dec 1995 into a national register were followed prospectively for disease progression, treatment and into a register for presence of CV risk factors. Of the patients 899 had donated DNA and were analysed for the genetic markers. The follow-up started at inclusion and ended at the first MI/AP, death or until Dec 31 2011 by co-analysing with the national registers of hospitalization and death in Sweden using classification of diseases (ICD-9 and 10). Genetic polymorphisms were analysed using Immunochip (SNP&SEQ Technology Platform Uppsala, Sweden). Univariate Cox regression and a likelihood ratio test was adopted to find SNPs most strongly associated with MI/AP. The potentially important (likelihood ratio p<0.05) clinical factors were also identified using univariate Cox regression. Selected clinical factors were combined with one SNP at the time in a multivariate Cox regression model and a likelihood ratio test was adopted to assess whether the SNP added significant information to a model based on only the selected clinical factors.
Analysis using the Immunochip yielded 131,523 SNPs, whereof 44,367 independent SNPs were identified after linkage analyses. In total 795 patients are included in the statistical analyses (some are excluded due to many missing values in the genetic data). The total follow-up time was 5607 person years until first MI/AP after RA disease onset. 52 patients had experienced a MI or AP leading to intervention. The strongest SNPs related to MI/AP were rs241425 (p=3.02e-06), rs2239701 (p=8.12e-06), rs9262155 (p=8.62e-06), rs2269706 (p=1.41e-05), and rs222418 (p=3.08e-05). Besides sex and age, hypertension, previous CV event, HLA-shared epitope, and oral corticosteroids were indicated as important in univariate Cox models (p<0.05). Likelihood ratio p-values after adjusting for the clinical factors were slightly lower than in the univariate models; rs241425 (p=1.04e-04), rs2239701 (p=4.75e-04), rs9262155 (p=9.20e-05), rs2269706 (p=5.55e-05), and rs222418 (p=1.87e-04).
SNPs analysed by Immunochip could be associated with MI/AP in patients with RA unrelated to more traditional risk factors.
S. Wållberg Jonsson,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/are-genetic-markers-associated-with-myocardial-infarction-in-patients-with-early-rheumatoid-arthritis/