Restricted accessResearch articleFirst published online 2025-5
Significant association of functional variants in the promoter sequence of IL18 with disease susceptibility and systemic lupus erythematosus clinical parameters
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex etiology. Interleukin-18 (IL-18) possesses pro-inflammatory properties and plays a central role in the development of SLE. In this study, we assessed the association between two functional variants that affect the expression of IL-18, namely −607C > A (rs1946518) and −137G > C (rs187238), and the risk of SLE development.
Methods
As a case-control study, 251 peripheral blood samples were collected from 121 SLE patients and 130 healthy participants. Genotyping of these polymorphisms was performed using the high-resolution melting (HRM) method, which employs real-time polymerase chain reaction.
Results
Our findings revealed a significant association between the AA genotype and A allele in rs1946518, showing a decreased risk of SLE (AA vs CC; OR: 0.386; 95% CI [0.174–0.828], A vs C; OR: 0.548; 95% CI [0.369–0.809]). Analogously, the CC genotype and C allele in rs187238 exhibited a similar trend (CC vs GG; OR: 0.240; 95% CI [0.055–0.803], C vs G; OR: 0.604; 95% CI [0.390–0.928]), indicating a reduced risk of SLE Moreover, SLE subjects with the protective allele in rs1946518 (AA + AC) demonstrated significantly lower levels of CRP, and Anti-dsDNA, suggesting lower disease activity. These patients also had a later age of onset, and a lower incidence of renal involvement and creatinine levels, indicating milder disease severity (p < .05).
Conclusion
The study indicates a significant relationship between the rs1946518 and rs187238 variants in IL-18 and a reduced risk of SLE. Furthermore, rs1946518 was found to be associated with certain clinical features related to disease activity and severity.
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