STAT4 Risk Allele Increases Lupus Nephritis, Heart Attack Risk in SLE Patients Who Smoke

Patients with systemic lupus erythematosus who carry the rs11889341 STAT4 risk allele are at a greater risk of lupus nephritis and myocardial infarction if they smoke, according to a study published online ahead of print in the Annals of the Rheumatic Diseases.

Findings stemmed from a discovery cohort of 776 patients with lupus from Sweden and a replication cohort of 836 patients with lupus from Norway and Denmark who underwent genotyping with the 200K Immunochip single nucleotide polymorphisms array (Illumina) and a custom array.

In the discovery cohort, patients with the risk allele who smoked had a 1.47 odds ratio for lupus nephritis compared with patients with lupus and the risk allele who did not smoke, according to the study. In the replication cohort, the odds ratio of lupus nephritis in patients with the risk allele who smoked was 1.84.

Meta-analysis of the 2 cohorts found each STAT4 risk allele increased lupus nephritis risk by about 50% in patients who smoked, researchers reported. However, there was no increased risk for patients who did not smoke.

The study also found patients with the STAT4 risk allele who smoked were at an increased risk of myocardial infarction. In the discovery cohort, those with any rs11889341 STAT4 risk allele had  a 2.72 odds ratio for myocardial infarction, and those with two risk alleles had an 8.27 odds ratio for heart attack. The odds ratio in the replication cohort for patients with the risk allele who smoked was 6.19.

“Our results stress the importance of smoking cessation in systemic lupus erythematosus and particularly among those carrying this risk allele,” researchers wrote.

—Jolynn Tumolo

Reference

Reid S, Hagberg N, Sandling JK, et al. Interaction between the STAT4 rs11889341(T) risk allele and smoking confers increased risk of myocardial infarction and nephritis in patients with systemic lupus erythematosus. Ann Rheum Dis. Published online ahead of print, March 25, 2021.