Toll-like receptor 5 and Toll-like receptor 9 single nucleotide polymorphisms and risk of systemic lupus erythematosus and nephritis in Egyptian patients

Abstract

Background Toll-like (TLRs) play a crucial role in both adaptive and innate immunity. The aim of the present study was to assess the association of TLR5-rs5744168, TLR9-rs187084, and TLR9-rs352140 single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) in Egyptian patients. Results The C allele and homozygous CC genotype of the TLR9-rs352140 in co-dominant and recessive models were more prevalent in SLE patients than controls (P = 0.047, P = 0.017, and P = 0.005 respectively). In contrast, allelic and genotyping distribution of TLR5-rs5744168 and TLR9-rs187084 SNPs showed no association with the risk of SLE. The T allele of the TLR5-rs5744168 was more prevalent in LN patients than controls (P = 0.021). The homozygous TT genotype of TLR5-rs5744168 SNP was more prevalent in LN patients in the co-dominant and the recessive models than controls (P = 0.036 and P = 0.011 respectively). The C allele of the TLR9-rs352140 was more prevalent in LN patients than controls (P = 0.015). The homozygous CC genotype of the TLR9-rs352140 SNP was more prevalent in LN than controls in co-dominant and recessive models (P = 0.002 and P < 0.001). In the recessive model of the TLR5-rs5744168 SNP, the TT genotype was found in 3.2% of the SLE patients while none of the SLE patients without LN or controls had TT genotype (P = 0.036). Also, in the recessive model of the TLR9-rs352140 SNP, the CC genotype was significantly more frequent in SLE patients with LN than without LN (44.4% vs 29.9%, P = 0.045). Conclusion Our results support the potential role of TLR5-rs5744168 SNP and TLR9-rs3532140 SNP not only in increasing the risk for development of SLE, but also in increasing the risk of LN in SLE patients among the Egyptian population.

Toll-like receptor 9 (TLR9) genetic variants rs187084 and rs352140 confer protection from Behcet’s disease among Iranians

“…Genome-wide association studies (GWAS) support that single nucleotide gene polymorphisms might predispose individuals to such autoimmune diseases [ 31 ]. Recently some studies were published to point out the possible role of TLR9 genetic variants rs352140 and rs187084, in the pathogenesis of some autoimmune diseases such as SLE, RA, AS, AML, and GD [ 17 ]- [ 24 ]. Here, in line with these studies, an association between rs352140 and rs187084 polymorphisms and BD was found among the Iranian population.…”

“…Besides, autoantibody production and induction of inflammatory cells are modulated through the TLR9 signaling pathway [ 14 – 16 ]. Previous studies have revealed the importance of TLR9 gene variants in the pathogenesis of autoimmune diseases such as Systemic lupus erythematosus (SLE) [ 17 – 19 ], rheumatoid arthritis (RA) [ 20 ], ankylosing spondylitis (AS) [ 21 ], acute myeloid leukemia (AML) [ 22 ], Hashimoto’s autoimmune thyroiditis [ 23 ], and Graves’ disease (GD) [ 24 ]. However, their possible association with BD has provided controversial results [ 24 ].…”

“…However, their possible association with BD has provided controversial results [ 24 ]. TLR9 rs187084 and rs352140 are located at the promoter region and second exon, respectively, where they regulate TLR9 expression [ 17 , 25 ]. These SNPs are the most functional and their special genotypes might lead to changes in TLR9 gene expression.…”

Systemic lupus erythematosus: latest insight into etiopathogenesis

“…TLRs are overstimulated on innate cells from SLE patients and their activation has been linked with SNP (Fig. 3 ), where specifically the polymorphism in TLR 5 and 9 were found to be associated with a higher risk of nephritis and SLE in the Egyptian population [ 53 ]. Polymorphism in DNMT3B (Fig.…”