Association Analysis of STAT-4 Gene Polymorphism in Rheumatoid Arthritis & Type 2 Diabetes Mellitus in Pakistani Patients

Abstract

Diabetes mellitus is defined as reduced insulin synthesis and action. It is marked by gradual loss of β-cell function and persistent insulin resistance. Lately, there is an overwhelming mystery that chronic low-grade inflammation and activated immune system are responsible for the pathogenesis and initiation of diabetes mellitus type 2. Rheumatoid arthritis is a persistent, systemic autoimmune disorder, which causes inflammation and joint damage linked to structural, bone and metabolic comorbidity. This study was carried out in 274 participants (T2D = 111, RA = 110, Controls = 53) in total to test STAT-4 prevalence (rs7574865). In order to enforce the target SNPs and examine their polymorphism in the Pakistani population, allele- specific polymerase chain reaction was performed. Between STAT-4 (rs7574865), T2DM and RA a significant correlation was noticed. The GT genotype indicates susceptibility of developing both RA and T2DM, in RA vs. control with OR= 2.97, 95% CI= 2.00 (1.20-3.33), P= <0.0001 whereas in T2DM with OR= 2.52, 95% CI= 1.84 (1.09-3.07), P= 0.0004. It indicates that the strong association of STAT4 rs7574865 with T2DM and RA shows that both systemic conditions can be present as co-morbidities. The STAT4 rs7574865 allelic distribution reveals that there is a significant distribution of T allele in RA, T2DM, and Control which indicates that T2D and RA patients who are homozygous for the T allele are susceptible to have increased disease activity and severity. However, more studies are still needed for the same population on larger scale to prove the relation of this polymorphism and both the severity and activity of RA and T2D.