Association study of a single nucleotide polymorphism in the exon 2 region of toll-like receptor 9 (TLR9) gene with susceptibility to systemic lupus erythematosus among Chinese

Abstract

Toll-like receptor 9 (TLR9) plays an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLR9 have been reported to be associated with a range of immune-related diseases, such as asthma, systemic lupus erythematosus (SLE) and so on. Family-based association analysis was performed to further investigate whether a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene is associated with susceptibility to SLE in a Chinese population. A total of 77 patients with SLE from 74 nuclear families, aged from 12 to 63 years, were enrolled according to 1997 criteria of American College of Rheumatology (ACR), 211 family members of these patients were also included. Genotyping was performed by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Among 77 patients with SLE, the CC, CT and TT genetype frequencies of the SNP (rs352140) were 20.8, 61.0 and 18.2%, respectively. Single loci analysis suggested that the T allele at position of rs352140 was significantly associated with the susceptibility to SLE (Z = 2.357, P = 0.018402) in dominant model, but not in additive or recessive model. Genetype analysis showed that individuals with CT genetype had greater susceptibility to SLE than those without (Z = 2.004, P = 0.045067). Our study suggests that a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene may be a susceptibility factor for SLE in Chinese population.

Toll-like receptor 9 SNPs are susceptible to the development and progression of membranous glomerulonephritis: 27 years follow-up in Taiwan

“…[27][28][29] In our study, we focused on variants of the TLR9 gene (rs352139 and rs352140) that have previously been associated with SLE. 30 Our study has demonstrated a statistically significant association between MGN and the rs352139 and rs352140 polymorphisms of TLR9, whereby the frequencies of the AA genotype at rs352139 and the GG genotype at rs352140 were significantly higher in MGN patients than in control participants. It is estimated from our results that the A-G haplotype of the TLR9 gene is present in approximately 68.7% of MGN patients.…”

Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice

“…This increased viral load might serve as a source of TLR9 stimulus in these patients, leading to some of the pathologic findings. MAS is recognized also as a complication of systemic lupus erythematosus (34), a disease that has been linked to TLR9 overstimulation by self DNA (35)(36)(37)(38). Patients with SJIA, another population at risk for MAS, show gene expression profiles consistent with repeated TLR/ IL-1 receptor activation (10).…”

The T-1237C Polymorphism of the Toll-like Receptor-9 Gene Is Associated with Chronic Kidney Disease in a Han Chinese Population

“…In particular the T-1237C SNP is associated with an increased risk for asthma in European and American populations (Lazarus et al 2003) and Crohn's disease in a German population (Torok et al 2009). TLR-9 G1635A SNP appears to play a role in susceptibility to SLE (Xu et al 2009) and in relation to renal disease, TLR-9 gene polymorphisms are associated and the histologic severity of disease in Japanese patients with IgA nephropathy (Suzuki et al 2008). …”