TLR7/8基因多态性与江苏省汉族人群哮喘发病风险及严重度的关系

山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (2): 93-98.

TLR7/8基因多态性与江苏省汉族人群哮喘发病风险及严重度的关系

张倩1，2，钱粉红3，周林福4，韦国桢1，柏建岭5，殷凯生4，施毅2

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. 南京军区南京总医院呼吸科，南京 210002； 3. 江苏大学附属江滨医院呼吸科，江苏镇江 212001；
4. 南京医科大学第一附属医院呼吸科，南京 210029；
5. 南京医科大学公共卫生学院流行病与生物统计学教研室，南京 210029

收稿日期:2012-07-18 出版日期:2013-02-10 发布日期:2013-02-10
通讯作者: 施毅（1956- ），男，教授，主任医师，博士生导师，主要从事肺部感染与慢性气道炎症性疾病的研究。E-mail: shiyi56@126.com
作者简介:张倩（1973- ），男，博士，副主任医师，主要从事支气管哮喘的基础与临床研究。E-mail: kezhang0601@163.com
基金资助:
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）；常州市卫生局青年基金（QN200904）

Association of TLR7/8 polymorphisms with risk and severity of asthma in Han population of Jiangsu province of China

ZHANG Qian1，2, QIAN Fen-hong3, ZHOU Lin-fu4, WEI Guo-zhen1,BAI Jian-ling5, YIN Kai-sheng4, SHI Yi2

1. Department of Respiratory Medicine, Changzhou No.2 People′s Hospital Affiliated to Nanjing Medical University, Changzhou 213003, Jiangsu, China;
2. Department of Respiratory Medicine, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China；
3. Department of Respiratory Medicine, Jiangbin Hospital Affiliated to Jiangsu University, Zhenjiang 212001, Jiangsu, China;
4. Department of Respiratory Medicine, First Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China;
5. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China

Received:2012-07-18 Online:2013-02-10 Published:2013-02-10

摘要/Abstract

摘要：

目的探讨Toll样受体7、8(TLR7/8)单核苷酸多态性在江苏省汉族人群中与哮喘发病危险性和哮喘相关表型的关系。方法收集哮喘患者318例为哮喘组，正常人352例为对照组。挑选TLR7 rs5935436， TLR8 rs3761623 和rs3764880三个多态位点，采用多重PCR结合标签阵列单碱基技术（SNPstream）进行基因分型。采用ELISA法测定血浆总IgE水平。结果 rs5935436 T等位基因是男性哮喘的保护因素，rs5935436 T等位基因分布频率在男性对照组中大于男性哮喘组（5.50%比0.74%，校正OR=0.126，95%CI=0.016~0.995，P=0.049）。男性无过敏性鼻炎的哮喘患者中rs3761623 G等位基因分布频率明显升高（校正OR=3.782，95%CI=1.022~14.045，P=0.047），而女性有过敏性鼻炎的哮喘患者中rs5935436 CT/TT 基因型分布频率明显降低（校正OR=0.180，95%CI=0.041～0.902，P=0.037）。rs3761623 AA基因型和rs3764880 GG基因型与女性哮喘患者的低FEV1%有关，并且与女性哮喘患者的严重度分级呈正相关。单倍型分析也有相同结果。结论 TLR7/8单核苷酸多态性与哮喘密切相关，而且与性别有关，这对于筛选哮喘高危人群和哮喘预防有重要意义。

关键词: 基因，多态性；哮喘；Toll样受体；表型；特应症；江苏省;汉族人群

Abstract:

Objective To evaluate the effects of polymorphisms in TLR7 and TLR8 on asthma risk and asthma-related phenotypes in Han population of Jiangsu province of China. Methods We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers of Han population from the same area in Jiangsu province. Genotyping of the selected SNPs, TLR7 rs5935436， TLR8 rs3761623 and rs3764880 was performed using multiplex PCR combined with tagged array single base extension technology（SNPstream）. Total IgG level in serum was determined by ELISA. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results The T allele of rs5935436 SNP in TLR7 was a protective factor for males in developing asthma(adjusted OR=0.126, 95%CI=0.016-0.995, P=0.049). The G allele of the rs3761623 appeared more frequently in male asthmatics without allergic rhinitis (adjusted OR=3.782, 95% CI=1.02214.045, P=0.047), while the CT/TT genotype of the rs5935436 appeared less frequently in female asthmatics with allergic rhinitis (adjusted OR=0.180, 95%CI=0.041-0.902, P=0.037). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion TLR7/8 polymorphisms may play an important role in the pathogenesis of asthma, which is gender-dependent. This could be clinically useful to identify patients at risk of asthma and prevent the occurrence of asthma.

Key words: Gene, polymorphism; Asthma; Toll-like receptors; Phenotype;Atopy; Jiangsu province； Han population

中图分类号:

R562.1

张倩1，2，钱粉红3，周林福4，韦国桢1，柏建岭5，殷凯生4，施毅2. TLR7/8基因多态性与江苏省汉族人群哮喘发病风险及严重度的关系[J]. 山东大学学报(医学版), 2013, 51(2): 93-98.

ZHANG Qian1，2, QIAN Fen-hong3, ZHOU Lin-fu4, WEI Guo-zhen1,BAI Jian-ling5, YIN Kai-sheng4, SHI Yi2. Association of TLR7/8 polymorphisms with risk and severity of asthma in Han population of Jiangsu province of China[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 93-98.

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