Unveiling the Role of Tlr9 Promoter Variants in Susceptibility and Clinical Features of Systemic Lupus Erythematosus Publisher Pubmed



Soleimani F ; Karbalaei Musa H ; Hajali M H ; Kenarangi T ; Mosallaei M ; Ansari N
Source: Lupus Published:2026

Abstract

Objective: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease in which dysregulated nucleic acid sensing and type I interferon responses drive autoantibody production and organ damage. Toll-like receptor 9 (TLR9) regulates these pathways, and promoter variants (rs187084 and rs5743836) may alter TLR9 expression and modulate disease susceptibility and severity. This study evaluated the association of these promoter SNPs and their haplotypes with SLE risk and clinical/laboratory features in an Iranian population. Methods: In this case–control study, we genotyped TLR9 promoter SNPs rs187084 and rs5743836 in 140 SLE patients and 140 age- and sex-matched healthy controls using the real-time PCR-high resolution melting (PCR-HRM) assay. Results: Our analysis showed that the CC and CT genotypes and the C allele of the rs5743836 SNP were associated with an increased risk of SLE (P < 0.05). However, there was no association between the rs187084 SNP and the risk of SLE (P > 0.05). The combined rs187084–rs5743836 CC haplotype was associated with increased SLE risk (CC vs TT haplotype, P < 0.001). Furthermore, in the patient group, carriers of the C allele in both promoter variants exhibited earlier disease onset and more active and severe disease, as evidenced by higher levels of C-reactive protein (CRP) and anti-dsDNA, reduced complement C3 and C4, and a higher frequency of renal and neurological complications (P < 0.05). Conclusion: Our data suggest that promoter variation in TLR9, specifically the rs5743836 C allele and the combined rs187084-rs5743836 CC haplotype, is linked to an increased risk of SLE and more disease activity and severe clinical presentation. © The Author(s) 2026