Prevalence of autoimmune diseases is 3-5% in the general population (1, 2). Observation of poly-autoimmunity (more than one autoimmune disease in the same person) and/or familial autoimmunity (more than one autoimmune disease in the same family) have suggested that autoimmune diseases share some genetic risk factors and biological pathways (3). Consistent with this observation, some genetic loci/genes have been found to be associated with multiple autoimmune diseases such as 6p21/MHC, 2q33/CTLA4, 2q32/STAT4, 18p11/PTPN2, 1q32/IL10, 7q32/IRF5, 1p31/IL23R (4). These shared loci/genes may influence the susceptibility for different diseases through the effects of the same or different genetic variations (5-7).
Rheumatoid arthritis (RA) is a complex, systemic, chronic, inflammatory, autoimmune disease characterized by synovial inflammation of mainly small joints and autoantibodies production, which may lead to physical disability associated with the socioeconomic burden and in severe cases, an early death (8, 9). The interplay of genetic and environmental factors triggers the onset of RA with an estimated heritability of ~60% (10). Multiple genome-wide association studies (GWAS), have identified ~50 genetic loci for RA susceptibility (11), with a major contribution from the MHC locus (12).
Type1 diabetes (T1D) is an autoimmune disease characterized by hyperglycemia due to the attack of body’s own immune system on β-cells in the pancreatic islets, reducing the production of insulin which may lead to major health issues such as heart disease, kidney failure, ketoacidosis, blindness and stroke (13, 14). Contrary to many other autoimmune diseases, which predominantly affect women, T1D affects both genders with a moderately higher prevalence in males at a relatively young age (15). According to epidemiological data, the incidence of T1D varies globally (16). To date more than 40 genetic loci have been found to be associated with T1D risk (17).
The concurrence of T1D and RA have been reported within the same individuals and families; however, the shared genetic factors between these two conditions are not fully identified. HLA-DRB1 in the MHC class II region is a major shared genetic locus between these two diseases(18, 19). Among non-MHC loci, PTPN22, AFF3, CTLA4, TNFAIP3 and TAGAP have been reported as shared risk loci between T1D and RA (20-22). A previous study conducted in a small set of RA Pakistani sample reported seven T1D-implicated risk variants to be associated with RA risk (23). In order to replicate or refute this reported association, the present study was conducted in a much larger Pakistani RA case-control sample on the same seven T1D-implicated risk variants.