Novel Gene Variants Associated With CVD Identified in Patients With SLE and RA

The interleukin 19 (IL-19) risk allele is associated with the development of stroke and myocardial infarction (MI) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), but not in the general population, which suggests that shared mechanisms may be involved in the cardiovascular disease (CVD) pathogenesis observed in patients with inflammatory rheumatic disorders, according to the results of a cohort study published in the Annals of the Rheumatic Diseases.

The investigators sought to explore whether single nucleotide polymorphisms at autoimmunity risk loci were linked to the development of CVD in patients with SLE and RA. The discovery cohort included a total of 1045 patients with SLE from rheumatology clinics in Sweden. The replication cohort from the University of California, San Francisco, included a total of 1043 patients from a second SLE cohort and an RA cohort with 824 patients.

There were 2 new putative risk loci associated with an elevated risk for CVD in 2 populations of patients with SLE, which persisted after adjustment for traditional CVD risk factors. An IL-19 risk allele, rs17581834(T), was significantly associated with stroke and MI in patients with SLE (odds ratio [OR], 2.3; 95% CI, 1.5-3.4; P =8.5´10⁻⁵), patients with RA (OR, 2.8; 95% CI, 1.4-5.6; P =3.8´10⁻³), and the meta-analysis of SLE and RA (OR, 2.5; 95% CI, 2.0-2.9; P =3.5´10⁻⁷), but not in the population controls.

The researchers found that the IL-19 risk allele affected protein binding, and patients with SLE with the risk allele had significantly increased levels of plasma-IL-10 (P =.004) and antiphospholipid antibodies (P =.01). Moreover, an SRP54-AS1 risk allele, rs799454(G), was significantly associated with stroke and transient ischemic attack in participants with SLE (OR, 1.7; 95% CI, 1.3-2.2; P =2.5´10⁻⁵), but not in participants with RA.

The investigators concluded that shared immune pathways may be implicated in the CVD pathogenesis reported among patients with inflammatory rheumatic diseases, an assumption that warrants further exploration.

Reference

Leonard D, Svenungsson E, Dahlqvist J, et al. Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis [published online March 7, 2018]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2017-212614