Toll-like receptor 4 polymorphisms in gram-negative bacterial infections of Han Chinese neonates.

Abstract

Human toll-like receptor 4 (TLR4) is an important receptor in innate immunity, particularly against gram-negative bacterial infection (GNBI). In our study, we evaluated associations of TLR4 single nucleotide polymorphisms (SNPs) with GNBI in Han Chinese neonates. Polymorphisms in TLR4 were genotyped in 201 neonates with GNBI and 279 gestational age and birth weight-matched controls without GNBI. Polymorphism analyses were applied to allele frequencies of the detected TLR4 SNPs and their associations with various clinical entities, including premature birth and GNBI were assessed. A total of six SNPs with more than 5% frequency were found in several promoter sequences, including rs10759931, rs2737190, rs10116253, rs10983755, rs1927914, and rs10759932. Mutation allele frequencies ranged from 23 to 41%. There were no SNPs with a frequency greater than 5% in exon analyses. Allele G rs2737190 mutations and GGCGGC haplotypes were more frequent among preterm GNBI neonates (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.02-1.71 and OR, 1.89; 95% CI, 1.19-3.00, respectively). No specific alleles or haplotypes were associated with GNBI status among term neonates. In this study population of Han Chinese, there was a significant association between an ethnical unique SNP in the TLR4 promoter region and preterm neonatal GNBIs.