Reid S, Hagberg N, Sandling JK, et al. - In the presence of the STAT4 risk gene variant, there appeared an increased risk of myocardial infarction (MI) and nephritis in systemic lupus erythematosus (SLE) in correlation with smoking. The IL12−STAT4 pathway is involved in SLE-cardiovascular morbidity.

• The 200K Immunochip single nucleotide polymorphisms (SNP) Array (Illumina) and a custom array were used for genotyping in patients with SLE.

• Analysis was performed on 60 SNPs with SLE association.

• Smoking was linked with MI; patients carrying any rs11889341 STAT4 risk allele or two risk alleles exhibited a greater effect.

• An increased risk of nephritis was also evident in smokers carrying the risk allele.

• Further increase in the risk of MI and nephritis was observed because of the interaction between smoking and the STAT4 risk allele.

• 54% (MI) and 34% (nephritis) of the risk was attributable to the interaction.

• Smokers had higher levels of interleukin-12-induced phosphorylation of STAT4 in CD8+ T cells.

• The IL12A rs564799 risk allele exhibited correlation with MI.