Polymorphisms in toll-like receptor 4 gene are associated with asthma severity but not susceptibility in a Chinese Han population.

BACKGROUND AND OBJECTIVES The toll-like receptor 4 (TLR4) gene links human innate immunity and adaptive immunity via bacterial endotoxin recognition, and plays a considerable role in the pathogenesis of asthma. The effects of the genetic variants of TLR4 on asthma are still largely unknown. This study aimed to evaluate the effects of TLR4 polymorphisms on asthma risk and asthma-related phenotypes in a Chinese Han population. METHODS We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers. Four tagging single nucleotide polymorphisms (SNPs) in the TLR4 gene were detected using GenomeLab SNPstream or TaqMans Genotyping. We conducted case-control and case-only studies to investigate the association between the selected tagging SNPs in TLR4 and asthma and asthma-related phenotypes. RESULTS We found no evidence to support a significant association between TLR4 SNPs and asthma susceptibility. However, our results revealed that the TT homozygote of rs1927914 was associated with lower forced expiratory volume in the first second (percent predicted) in asthmatic patients. An evidently positive association was found between asthma severity and both the TT genotype of rs1927914 and the GG genotype of rs10983755 and rs1927907 (P = .024, P = .009, and P = .013, respectively), indicating that the C allele of rs1927914 and the A allele of rs10983755 and rs1927907 have a protective effect on asthma severity. CONCLUSION TLR4 polymorphisms do not contribute to asthma susceptibility but they may influence the severity of asthma.