The association of STAT4 single nucleotide polymorphisms with thrombotic manifestations in a cohort of patients with autoimmune diseases and antiphospholipid antibodies

Objective: To assess the association of genetic polymorphisms of signal transducer and activator of transcription ( STAT ) 4 with thrombotic manifestations in patients with autoimmune diseases, including antiphospholipid syndrome (APS). Methods: A group of 395 adult, non-related patients (331 women and 64 men) with autoimmune diseases and 150 healthy control subjects were genotyped for 4 STAT4 single-nucleotide polymorphisms (SNPs): rs7574865, rs10181656, rs7582694 and rs11684030. The risk alleles associations with antiphospholipid antibodies (APLA) and the occurrence of thrombotic events were then analysed in the group of patients. Results: Among 395 patients almost half were diagnosed with APS: 97 with primary (PAPS) and 83 with secondary (SAPS). Differences in frequencies of the risk alleles for the following 3 SNPs: G/C rs7582694, rs10181656 C/G, and rs7574865 G/T were stronger associated with APS than with systemic lupus erythematosus or other autoimmune diseases. All 3 SNPs were associated with prothrombotic, triple positive APLA profile: OR = 1.68 (1.04 to 2.70, 95% CI), p = 0.032; OR = 1.61 (1.1 to 2.59, 95% CI), p = 0.048; and OR = 1.61 (1.0 to 2.59, 95% CI), p = 0.048; respectively. The association of the 2 STAT4 risk alleles, i.e., SNP rs7582694 (C) and rs10181656 (G) was stronger for venous thromboembolism: OR = 1.6 (1.1 to 2.5, 95% CI), p = 0.03 and OR = 1.5 (1.1 to 2.5, 95% CI), p = 0.02; respectively. Conclusions: SNPs in the STAT4 gene, i.e., rs7582694(C), rs1018165(G), and rs7574865(T) are associated with venous thromboembolic events in autoimmune disease patients, therefore they might identify subjects at risk of venous thromboembolism.