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

Abstract 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.