Role of innate immune receptors TLR4 and TLR2 polymorphisms in systemic lupus erythematosus susceptibility

Abstract

Aim: Through their recognition of various bacterial cell wall components, TLR2 and TLR4 participate in the innate response and modulate the activation of adaptive immunity. Therefore, the genetic background of these receptors might play a crucial role in autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated the possible association between polymorphisms within TLR2 and TLR4 genes with SLE susceptibility. Material and methods: A total of 100 SLE patients and 200 unrelated healthy controls of the Tunisian population were enrolled in the study.TLR4rs4986790, TLR4rs4986791, and TLR2rs5743708 genotyping were performed using a polymerase chain reaction-restriction fragment length polymorphism method. The number of guanine-thymine (GT) repeat microsatellite in the intron 2 of TLR2 gene was analyzed by sequencing. Results:We reported a lack of allelic and genotypic association between SNPs of TLR4 and TLR2 genes and SLE pathogenesis. No correlation was found with any SLE features. However, SLE susceptibility was associated with the GT repeat microsatellite polymorphism in the human TLR2 gene. Further subclassification of alleles into three subclasses revealed a significant association between the long-sized repeats ((GT) >23) and SLE. Conclusion: Though the results showed the absence of genetic association of TLR4 and TLR2 SNPs with the risk of developing SLE, we have identified a protective association between the microsatellite polymorphism in intron 2 of the TLR2 gene and SLE. Functionally, these (GT)n repeats may confer modifying effects or susceptibility to certain inflammatory conditions.

Associations of toll-like receptor polymorphisms with systemic lupus erythematosus: A meta-analysis

“…A total of 667 articles were identified using both computerized and manual search strategies, of which 22 met the criteria for full-text evaluation. Six of these articles were excluded as they lacked polymorphism data; therefore, the inclusion criteria were met by a total of 16 articles [ [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] ]. Two studies that met these criteria included data from two distinct groups receiving individual care [ 7 , 17 ].…”

“…Although the findings of these studies are unclear, it has been proposed that TLR7 rs179008, rs3853839, and rs1790010 polymorphisms may be risk factors for SLE. Similar studies have been conducted on TLR4 rs4986791 and rs798690 polymorphisms associated with SLE, with conflicting results [ [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] ].…”

Genetic variation in toll-like receptor 4 gene with primary antiphospholipid syndrome susceptibility: a cohort of Egyptian patients

“…Our data also corroborate previous studies that evaluated other autoimmune diseases in different populations. A study performed in the Tunisian population reported the prevalence of the A allele of the rs4986790 variant and C allele of the rs4986791 variant in patients with SLE and controls [41]. A separate study conducted in the Hungarian population assessed the association of TLR4 Asp299Gly &Thr399Ile polymorphisms with ankylosing spondylitis (AS) and reactive arthritis (ReA) and found no significant difference in allele or genotype frequencies between controls and patients with AS or ReA.…”

Predicted Immune-Related Genes and Subtypes in Systemic Lupus Erythematosus Based on Immune Infiltration Analysis

“…The role of toll like receptor 2 TLR2 has been well investigated in SLE initiation in context of pathogen recognition and autoantibody production to self-DNA antigens [ 39 ]. Furthermore, PMBC bound TLR2 has been shown as marker of disease activity in SLE [ 40 ] and SLE susceptibility has been found to be associated with TLR2 gene polymorphism [ 41 ]. TSR2 is known to inhibit nuclear factor- κ B transcription and induce apoptosis [ 42 ].…”