Association of STAT4 polymorphism with susceptibility and severity of rheumatoid arthritis and systemic lupus erythematosus in Egyptian patients

Abstract

The link between rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and gene polymorphism of the signal transducers and activators of transcription 4 (STAT4) has been proved in different populations. Investigation of the possible association of STAT4 rs7574865(G/T) polymorphism with RA and SLE patients and the significance of its relation to the diseases activity and severity. Fifty RA patients, 50 SLE patients and 50 healthy controls were included. STAT4 genotyping was performed by restriction fragment length polymorphism–polymerase chain reaction. In both RA and SLE patients, the frequencies of STAT4(GT) genotype were significantly increased compared to controls (46%,48% and 26% respectively). There was a significant difference in the distribution of the T allele between RA and SLE patients with the controls (37%, 40% vs 17%). Patients carrying the T-allele had a high risk for RA and SLE in comparison with the healthy control (p = 0.0001). RA patients with the TT genotype had significantly higher levels of the erythrocyte sedimentation rate, C-Reactive protein, anti-cyclic citrullinated peptide, disease activity score (DAS28) and modified Sharp/van der Heijde score compared to those with GG and GT genotypes. The TT genotype in SLE significantly correlated with low complement (C3,C4), proteinuria, anti-double stranded deoxyribonucleic acid (dsDNA), photosensitivity and damage index. STAT4 polymorphism was associated with an increased risk of RA and SLE patients, so it may be a common genetic risk factor for both diseases. Moreover RA, SLE patients who are homozygous for the T-allele are susceptible to have increased disease activity and severity.