Identifying the Link Between IRAK1 Genetic Variations (rs1059703, G/A and rs7061789, G/A) and Vulnerability to Rheumatoid Arthritis

Abstract Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammatory processes. Objectives: This study focuses on identifying specific genetic variations (gene polymorphisms) in the interleukin-1 receptor-associated kinase (IRAK1) that plays a role in RA. Previous research has produced conflicting outcomes regarding the functional implications of these genetic variations. Materials and Methods: The research involved 200 individuals diagnosed with RA based on ACR criteria and 200 healthy controls in a case-control design. Genomic DNA was extracted from frozen blood samples collected in EDTA tubes. For DNA extraction, a spin column method and Add Prep Genomic DNA Extraction Kit (Add Bio, Korea) were used. Two specific variations in IRAK1 (rs1059703 G>A and rs7061789 G>A) were genotyped. The genotypes and allele frequencies of these variations were subjected to a chi-square test to determine their potential contribution to RA susceptibility. Results: The study identified a significant association between the rs1059703 A allele and an increased risk of RA. Specifically, individuals with AA and GA genotypes exhibited higher susceptibility (odd ratio [OR] = 2.5, 95% confidence interval [95% CI] = 1.83–3.4, P = 0.0001) to the rs1059703 G/A polymorphism. This risk was evident in codominant, dominant, and over-dominant genetic models. The combined GA+AA genotypes had notably higher RA risk compared to the control group (adjusted OR = 3.21, 95% CI = 1.8–5.5, P = 0.0001) under the dominant pattern. In the over-dominant model, individuals with the heterozygous genotype (GA) exhibited increased RA risk (OR = 2.43, 95% CI = 1.71–3.9, P = 0.0001). ad ditionally, the study revealed significant differences in IRAK1 rs1059703 genotypes concerning clinical and laboratory features of patients. No significant association between rs7061789 G>A and the risk of RA ( P = 0.42). Conclusion: The findings highlight that the rs1059703 A allele (considered a risk allele) within the IRAK1 gene contributes to elevated susceptibility to RA, leading to greater disease severity and influencing the onset age of RA among Iraqi patients. While the rs7061789 SNP of IRAK1 did not demonstrate any impact on RA development within the studied Iraqi population.