Polymorphism Analysis as Biomarker in Genes AIRE, CD40, HLA-DRB1 and TRAF1/C5 SNPs in Rheumatoid Arthritis Patients

The main objective of the study was to determine the association of genes AIRE (rs2075876), CD40 (rs4810485), HLA-DRB1 (rs6457617) and TRAF1/C5 (rs10818488) polymorphisms with rheumatoid arthritis (RA) from the population of Pakistan. Blood samples of 300 RA patients and 300 healthy controls were taken from different hospitals in Pakistan. Extraction of DNA was carried out; a specific region of DNA was amplified using PCR. Polymorphic analysis was performed for genes AIRE (rs2075876), CD40 (rs4810485), HLA-DRB1 (rs6457617) and TRAF1/C5 (rs10818488). The demographic parameters, like age, showed statistically significant association and increased the risk of the disease up to 2-fold (odds ratio [OR] = 2.57; 95% confidence interval [CI] = 1.60–4.12; p = 0.0001). Gender and family history did not show any significant association with arthritis (OR = 1.12; 95% CI = 0.69–1.81; p = 0.6260; OR = 0.70; 95% CI = 0.44–1.11; p = 0.1313, respectively). In the case of smoking status, the difference was statistically significant for both smokers and non-smokers. In smokers, there was a decreased risk of RA (OR = 0.45; 95% CI = 0.28–0.73; p = 0.0011), and in non-smokers, there was an increased risk of disease up to 2-fold (OR = 2.17; 95% CI = 1.36–3.47; p = 0.0011). In AIRE gene, heterozygous (AG) of rs2075876 showed a highly significant association with increased risk of RA up to 3-fold (OR = 3.39; 95% CI = 2.08–5.54; p = 0.0001), whereas homozygous mutant (GG) also showed significant association (OR = 0.43; 95% CI = 0.26–0.72; p = 0.0014) but with decreased risk. In CD40 gene, heterozygous (AG) of rs4810485 showed significant association with a decreased risk of RA (OR = 0.59; 95% CI = 0.377–0.945; p = 0.027), whereas the homozygous mutant (GG) of rs4810485 showed highly significant association by increasing risk of up to 4-fold (OR = 4.318; 95% CI = 2.553–7.303; p = 0.0001). In HLA-DRB1 gene, heterozygous (CT) of rs6457617 showed significant association with a decreased risk of disease (OR = 0.52; 95% CI = 0.35–0.85; p = 0.007), whereas the homozygous mutant (TT) of rs6457617 showed highly significant association by increasing the risk of RA up to 4-fold (OR = 4.37; 95% CI = 2.55–7.47; p = 0.0001). In the TRAF1/C5 gene, heterozygosity (AG) of rs10818488 showed a significant association with an increased risk of disease up to 4-fold (OR = 4.06; 95% CI = 2.38–6.98; p = 0.0001). Highly significant associations of genes AIRE (rs2075876), CD40 (rs4810485), HLA-DRB1 (rs6457617) and TRAF1/C5 (rs10818488) polymorphisms were observed with RA.