[No authors listed]
Toll-like receptors (TLRs) are innate immune mediators that stimulate nuclear factor kappa B and the inflammatory cytokines. TLR1 is expressed in renal tubular epithelial cells when the kidney is injured, but the role of TLR1 gene in glomerulonephritis has not been clearly elucidated. We aimed to investigate the association of TLR1 polymorphisms with immunoglobulin A nephropathy (IgAN) in children. One hundred and ninety pediatric patients with biopsy-proven IgAN and 283 healthy control subjects were enrolled. Two single nucleotide polymorphisms of TLR1 gene [rs4833095 (missense, Asn248Ser) and rs5743557 (promoter, -414C/T)] were selected and genotyped by direct sequencing. For rs4833095, the C/T genotype in the codominant model (vs. the T/T genotype) [odds ratio (OR)â=â2.11, 95% confidence interval (CI): 1.21-3.69, Pâ=â0.009] and the genotype containing C allele (C/T and C/C) in the dominant model (vs. the T/T genotype) (ORâ=â1.97, 95% CI: 1.16-3.34, Pâ=â0.012) were associated with an increased risk of IgAN. For rs5743557, the T/T genotype in the codominant model (vs. the C/C genotype) (ORâ=â1.74, 95% CI: 1.02-2.96, Pâ=â0.041) appeared to be associated with IgAN risk. In haplotype analysis, the CT haplotype revealed an association with IgAN (codominant model, ORâ=â1.38, 95% CI: 1.06-1.80, Pâ=â0.017; dominant model, ORâ=â1.76, 95% CI: 1.16-2.67, Pâ=â0.008). After Bonferroni correction, the association of the genotypes of rs4833095 and the CT haplotype with IgAN risk remained significant. These findings suggest that TLR1 gene polymorphisms may affect IgAN susceptibility in Korean children.
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