TLR1 polymorphism rs4833095 as a risk factor for IgA nephropathy in a Chinese Han population: A case-control study

Abstract

Toll-like receptors (TLRs) are a family of transmembrane receptors, and play a vital role in recognizing invading pathogens and activating innate immunity. Previous studies indicated that TLR1 single nucleotide polymorphisms (SNPs) might be associated with the risk of IgA nephropathy (IgAN). This study aims to investigate the relationship between TLR1 SNPs (rs4833095 and rs5743557) and IgAN in a Chinese Han population. This case-control study included 351 patients with IgAN and 310 healthy controls. Two SNPs (rs4833095 and rs5743557) of TLR1 were genotyped by Sequenom MassARRAY. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. We found that both allele and genotype frequencies of rs5743557 were not associated with IgAN risk. Rs4833095 increased IgAN risk compared with controls in the allele, dominant and log-additive models (P = 0.04, 0.04 and 0.03, respectively). Further haplotype analysis revealed that the Trs4833095Trs5743557 haplotype may be a risk factor for IgAN (OR = 1.28; 95% CI = 1.01–1.63; P = 0.046). Furthermore, rs4833095 was associated with Lee's grades (OR = 1.75; 95% CI = 1.03–2.96; P = 0.04). However, there was no significant association between the genotype distributions of rs5743557 and clinical parameters of IgAN such as gender, 24 hour urine protein, blood pressure, and Lee's grades. Taken together, these findings suggest that the TLR1 rs4833095 polymorphism may play a role in the development and progression of IgAN.

Association of Immune and Inflammatory Gene Polymorphism With the Risk of IgA Nephropathy: A Systematic Review and Meta-Analysis of 45 Studies

“…However, the contradictory result was observed in Chinese Han population and Korean pediatric patients in IL-1B (rs1143627) (40, 41) (Supplementary Figure 6). Chinese population and Korean pediatric patients shared the same predisposition of rs4833095 and rs5743557 in TLR1which presented in (Supplementary Figure 7) (42,43) 10).…”

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

“…Genetic variation in TLRs has been associated with susceptibility and outcomes in a number of infectious and noninfectious disease states [35]. Association between TRL1 rs4833095 and tuberculosis susceptibility [36, 37], increased risk of IgA nephropathy [38], Crohn's disease and ulcerative colitis [39], susceptibility for alopecia areata [40], increased mortality in patients with sepsis following traumatic injury [35] have been found in various studies. The discovery of association between TLR1 SNP rs4833095 and H. pylori seroprevalence in a GWAS in European descent population [20] was replicated in the Thai population: the TLR1 rs4833095, C allele was associated with a significantly increased risk for H. pylori infection [19].…”

TLR1 polymorphisms are significantly associated with the occurrence, presentation and drug-adverse reactions of tuberculosis in Western Chinese adults

“…We also discovered that the rs5743557 A allele appeared to have a slight protective effect for TB infection. Published studies have shown that rs5743557, in the TLR1 promoter region, is not associated with the development of IgA nephropathy in a Chinese Han population [ 29 ] or benign prostatic hyperplasia in a Korean population [ 30 ], whereas it is significantly correlated with a high risk for childhood IgA nephropathy in a Korean population [ 18 ]. The data described above strongly indicate that various SNPs have different impacts on the development and progression of human disorders depending on iverse pathological conditions and ethnicity.…”