TLR4基因单核苷酸多态性与哮喘严重度及哮喘相关临床指标的关系  

Association between polymorphisms of Toll-like receptor 4 and asthma severity and asthma-related phenotypes

作　　者：鲁静洁[1] 钱粉红[2] 殷小伟[1] 殷凯生[3] 施毅[4] 张倩[1,4] 

机构地区：[1]南京医科大学附属常州第二人民医院呼吸科,江苏常州213003 [2]江苏大学附属江滨医院呼吸科,江苏镇江212001 [3]南京医科大学第一附属医院呼吸科,江苏南京210029 [4]南京军区南京总医院呼吸科,江苏南京210002

出　　处：《南京医科大学学报（自然科学版）》2013年第9期1231-1236,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81270077);中国博士后科学基金资助项目(2012T50894;2012M521936);江苏省医学重点学科开放课题(KF200920);常州市卫生局重大课题(ZD201002);常州市应用基础研究项目(CJ20122005);常州市卫生局重点医学创新人才项目资助

摘　　要：目的:探讨Toll样受体4(TLR4)单核苷酸多态性(SNPs)与哮喘发病严重度和哮喘相关临床指标的相关性。方法:在HapMap上挑选TLR4的全部标签SNPs。连续性招募哮喘患者318例。采用SNPstream和Taqmans法进行基因分型。流式细胞技术检测外周血中CD4+CD25high调节性T细胞及其表面TLR4的表达。结果:TLR4的4个标签SNPs rs1927914、rs10983755、rs11536879、rs1927907与哮喘患者外周血嗜酸性粒细胞、血清总IgE和hsCRP无相关性。但是rs1927914 TT基因型比TC和CC基因型的FEV1%要低(P=0.043),哮喘发病程度更严重(P=0.024)。同样,rs10983755 GG基因型比GA和AA基因型、rs1927907 GG基因型比GA和AA基因型哮喘发病程度更严重(P=0.009和P=0.013)。TLR4 SNPs与哮喘患者外周血CD4+CD25high调节性T细胞无相关性,但是和CD4+CD25high调节性T细胞表面TLR4的表达量有关。结论:TLR4 SNPs和哮喘严重度分级及CD4+CD25high调节性T细胞表面TLR4的表达量相关,与哮喘其他表型无相关性。TLR4 SNPs可能影响哮喘症状的严重度,这为哮喘的基因治疗提供了一定理论基础。Objective：To evaluate the effects of polymorphisms of Toll-like receptor 4 （TLR4） on asthma severity and asthma-related phenotypes in a Chinese Han population. Methods：Four tagging single nucleotide polymorphisms （SNPs） in TLR4 gene were detected using GenomeLab SNPstream or TaqMans Genotyping in 318 adult asthmatic patients. Peripheral CD4^＋CD25^high regulatory T cells and expression of TLR4 were detected by flow cytometry. Linear regression and Ordinal logistic regression,adjusted for age,gender,smoking status,inhaled corticosteroid treatment and SPT,were applied appropriately. A 2-sided P value 〈 0.05 was considered significant. Results：The distribution of each genetic variant met the conditions of the Hardy–Weinberg equilibrium （HWE）. We found no evidences supporting a significant association between TLR4 SNPs and eosinophil counts,serum hsCRP,total serum IgE levels in asthmatic patients. However,our results revealed that the TT homozygote of rs1927914 was associated with lower FEV1% in asthmatic patients. An evidently positive association was found between the TT genotype of rs1927914,or the GG genotype of rs10983755 and rs1927907,and asthma severity（P = 0.024,0.009,0.013,respectively）,which indicated that the C allele of rs1927914,and the A allele of rs10983755 and rs1927907 had a protective effect on asthma severity. Although no significant association between TLR4 SNPs and the CD4^＋CD25^high regulatory T cell counts in peripheral blood from asthmatic patients was found,the expression of TLR4 on the surface of CD4^＋CD25^high regulatory T cells was related to TLR4 SNPs. Conclusion：TLR4 polymorphisms may influence the severity of asthma. It could be clinically useful for gene therapy of asthma.

关 键 词：哮喘 单核苷酸多态性 CD4+CD25high调节性T细胞 TOLL样受体4 

分 类 号：R562.25[医药卫生—呼吸系统]