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Original Article


Polymorphisms in Toll-Like Receptor 4 Gene Are Associated With Asthma Severitymbut not Susceptibility in a Chinese Han Population


Q Zhang,1,* FH Qian,2,* LF Zhou,3,* GZ Wei,1 GF Jin,4 JL Bai,5 KS Yin3

1Department of Respiratory Medicine, Affi liated Changzhou No.2 People’s Hospital, Nanjing Medical University,
Changzhou 213003, China
2Department of Respiratory Medicine, Affi liated Jiangbing Hospital, Jiangsu University, Zhenjiang 212001, China
3Department of Respiratory Medicine, First Affi liated Hospital, Nanjing Medical University, Nanjing 210029, China
4Department of Epidemiology and Biostatistics, Cancer Research Center, Nanjing Medical University, Nanjing 210029, China
5Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China
*These authors contributed equally to this article.

J Investig Allergol Clin Immunol 2011; Vol. 21(5): 370-377



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 fi rst 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.

Key words: Asthma. Atopy. Phenotype. Polymorphism. Toll-like receptor 4.