The findings may open the door for early testing for coronary artery disease risk in patients with lupus, the researchers wrote.
“Here, we report the application of multiple, complementary [Mendelian randomization] methods to identify causal paths from SLE-associated variants to [coronary artery disease (CAD)] using summary statistics from genetic association studies,” Jessica Kain, PhD, of AMPEL BioSolutions, in Virginia, and colleagues wrote. “Understanding the pathogenesis of genetic variants underlying the increased CAD risk in SLE can ultimately provide insight into the immune and inflammatory components of atherosclerosis, as well as revealing opportunities for targeted therapies.”
To identify which genes might be associated with either or both diseases, Kain and colleagues obtained data from previous genome-wide association (GWAS) and Immunochip studies. The researchers collected single-nucleotide polymorphisms (SNPs) associated with SLE or CAD and, when looking for SNPs associated with SLE, included multiple genome-wide association and Immunochip studies in order to feature as many ancestries as possible.
Kain and colleagues identified expression quantitative trait loci and mapped them to the associated expression genes. In total, 7,222 unique SNPs associated with SLE, and 16,163 unique SNPs associated with CAD, were identified and used in the analysis.
According to the researchers, 96 SNPs were identified as being associated with both diseases. These SNPs were mapped to identify 189 unique genes encoding 135 proteins. Additional analyses demonstrated that the genes were “significantly enriched for genomic regions capturing the genetic heritability of CAD and CVD [P < .05],” the researchers wrote.
“New findings suggest that the causal relationship with SLE appears to be focused on the atherosclerotic process, evidenced by positive estimates with CAD, [myocardial infarction] and [ischemic stroke], but not other cardiac conditions such as cardiomyopathy or [atrial fibrillation],” Kain and colleagues wrote. “Moreover, a number of the immune and inflammatory pathways identified in these analyses would well contribute to the pathogenesis of CAD even in the absence of SLE or other recognized autoimmune conditions.”
According to Jane E. Salmon, MD, of the Hospital for Special Surgery, who was not involved in the study, the findings offer an opportunity for new treatment strategies to both prevent and treat atherosclerotic CVD in SLE.
“For the first time, AMPEL’s elegant CardioGENE work elucidates the genetic risk factors shared between patients with coronary artery disease and those with lupus, providing a new opportunity to consider novel therapeutic approaches to prevent and treat atherosclerotic CVD in patients with lupus,” Salmon said in a statement provided to Healio.