Polymorphism of some JAK-STAT pathway genes and its regulators in patients with systemic lupus erythematosus and lupus nephritis in Repubic of Belarus

Genes of interest – STAT4, PTPN2 and PTPN22 – are components of the JAK-STAT signaling pathway, one of the important regulators of the immune system. The JAK-STAT pathway plays a key role in the development of both systemic lupus erythematosus (SLE) and its manifestation, lupus nephritis (LN) by mediating interferon levels and promoting IFN-induced gene expression. We investigated the allele and genotypes frequencies at the polymorphic loci of the STAT4 (rs7574865, rs3821236), PTPN2 (rs2542151, rs7234029) and PTPN22 (rs2476601) genes in groups of children (n = 37) and adults (n = 63) with SLE and LN. The control group included children (n = 420) and adults (n = 345) without autoimmune diseases. The analysis of the combined group of pediatric and adult patients revealed that the rs7574865 polymorphic locus of the STAT4 gene is associated with the risk of developing SLE (Т: OR 1,99 [1,42–2,79], р = 0,0001; TT: OR 3,36 [1,64–6,87], р = 0,0018) and LN (Т: OR 1,91 [1,32–2,78], р = 0,0008; TT: OR 4,25 [2,02–8,95], р = 0,0004). These associations also persisted when analyzing the pediatric and adult groups of patients with SLE and LN separately. Moreover, the rs7574865 polymorphic locus of the STAT4 gene appears to be a common genetic risk factor for autoimmune diseases development. The association of the polymorphic locus rs2542151 of the PTPN2 gene with the SLE (G: OR 1,66 [1,12–2,47], p = 0,014; GT: OR 1,74 [1,10–2,77], р = 0,021) and LN (G: OR 1,87 [1,21–2,88], р = 0,006; GT: OR 1,90 [1,13–3,18], р = 0,017) susceptibility was also found in a combined group of patients. The polymorphic loci rs7234029 in the PTPN2 gene and rs2476601 in the PTPN22 gene were not associated with SLE or LN regardless of the age of the patients.