Liu Wen, Xu Li-Sheng, Liu Qi-Ji, Dong Fang-Zheng, Qiu Rong-Fang, Wen Ming-Chun, Han Yu-Ling, Tang Ning-Bo, Kang Li-Jun, Wu Jin-Xiang, Liu Fen, Zhao Ji-Ping, Yang Meng-Meng, Wang Jun-Fei, Ding Ming-Jie, Sun Yue-Mei, Fei Wen-Jian, Dong Liang
Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Exp Lung Res. 2012 Oct;38(8):375-82. doi: 10.3109/01902148.2012.714840. Epub 2012 Aug 22.
Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2(TH2) cells. Thymic stromal lymphopoietin (TSLP) can aggravate asthmatic lung inflammation by activating dendritic cells (DCs) to promote TH2 differentiation. TSLP promoter polymorphisms are associated with susceptibility to bronchial asthma in Japanese population. We sought to determine whether single nucleotide polymorphisms (SNPs) in TSLP gene are associated with asthma in Chinese Han population.
To analyze the polymorphism of the two SNPs Rs2289276 and Rs2289278 in TSLP gene and to evaluate the association between the two SNPs and asthma susceptibility in Chinese Han population by using case-control study.
five hundred and thirty one asthmatic patients and 540 age-sex matched normal controls were collected and DNA were extracted from peripheral blood, then the genotypes of SNPs Rs2289276 and Rs2289278 in TSLP gene were detected with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), genotype and allele frequencies were calculated and analyzed with Chi-square test.
Frequencies of CC/CT/TT genotypes at Rs2289276 site were 0.4706/0.4392/0.0902 in the asthmatic patients and 0.5604/0.3800/0.0595 in the healthy controls. Frequencies of CC/CG/GG genotypes at Rs2289278 site were 0.6502/0.2966/0.0532 in the asthmatic patients and 0.5795/0.3428/0.0777 in the healthy controls. The genotype and allele frequencies of the two SNPs in asthma patients were significantly different from those in the healthy controls. Rs2289278 C allele was correlated with decreased FEV(1): FVC (P ≤ .05).
TSLP variants are significantly associated with bronchial asthma. TSLP might be a new therapeutic target molecule for asthma.
哮喘是一种由辅助性T细胞2（TH2）介导的气道慢性炎症性疾病。胸腺基质淋巴细胞生成素（TSLP）可通过激活树突状细胞（DC）促进TH2分化，从而加重哮喘肺部炎症。TSLP启动子多态性与日本人群支气管哮喘易感性相关。我们旨在确定TSLP基因单核苷酸多态性（SNP）是否与中国汉族人群哮喘相关。
通过病例对照研究分析TSLP基因两个SNP（Rs2289276和Rs2289278）的多态性，并评估这两个SNP与中国汉族人群哮喘易感性之间的关联。
收集531例哮喘患者和540例年龄、性别匹配的正常对照，提取外周血DNA，采用聚合酶链反应和限制性片段长度多态性（PCR-RFLP）检测TSLP基因SNP Rs2289276和Rs2289278的基因型，计算基因型和等位基因频率，并用卡方检验进行分析。
哮喘患者中Rs2289276位点CC/CT/TT基因型频率分别为0.4706/0.4392/0.0902，健康对照中为0.5604/0.3800/0.0595。哮喘患者中Rs2289278位点CC/CG/GG基因型频率分别为0.6502/0.2966/0.0532，健康对照中为0.5795/0.3428/0.0777。哮喘患者中这两个SNP的基因型和等位基因频率与健康对照有显著差异。Rs2289278 C等位基因与FEV(1):FVC降低相关（P≤0.05）。
TSLP变异与支气管哮喘显著相关。TSLP可能是哮喘新的治疗靶点分子。
