Significant Association of Functional Variants in the Promoter Sequence of Il18 With Disease Susceptibility and Systemic Lupus Erythematosus Clinical Parameters Publisher Pubmed



Y Mohammadi YUSUF ; M Saghaei MOZHDEH ; M Saghi MOSTAFA ; Sa Mazhari Seyed AMIRHOSSEIN ; B Alani BEHRANG ; N Ehtesham NAEIM ; T Kenarangi TAIEBE ; M Soosanabadi MOHSEN
Source: Lupus Published:2025

Abstract

Objective: 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. © 2025 Elsevier B.V., All rights reserved.