TSLP 基因变异与混合人群哮喘的关系。
Genetic variants of TSLP and asthma in an admixed urban population.
机构信息
Department of Environmental Medicine, New York University School of Medicine, New York, New York, United States of America.
出版信息
PLoS One. 2011;6(9):e25099. doi: 10.1371/journal.pone.0025099. Epub 2011 Sep 22.
BACKGROUND
Thymic stromal lymphopoietin (TSLP), an IL7-like cytokine produced by bronchial epithelial cells is upregulated in asthma and induces dendritic cell maturation supporting a Th2 response. Environmental pollutants, including tobacco smoke and diesel exhaust particles upregulate TSLP suggesting that TSLP may be an interface between environmental pollution and immune responses in asthma. Since asthma is prevalent in urban communities, variants in the TSLP gene may be important in asthma susceptibility in these populations.
OBJECTIVES
To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population. METHODOLOGY AND MAIN RESULTS: Ten tag-SNPs in the TSLP gene were analyzed for association with asthma using 387 clinically diagnosed asthmatic cases and 212 healthy controls from an urban admixed population. One SNP (rs1898671) showed nominally significant association with asthma (odds ratio (OR) = 1.50; 95% confidence interval (95% CI): 1.09-2.05, p = 0.01) after adjusting for age, BMI, income, education and population stratification. Association results were consistent using two different approaches to adjust for population stratification. When stratified by smoking status, the same SNP showed a significantly increased risk associated with asthma in ex-smokers (OR = 2.00, 95% CI: 1.04-3.83, p = 0.04) but not significant in never-smokers (OR = 1.34; 95% CI: 0.93-1.94, p = 0.11). Haplotype-specific score test indicated that an elevated risk for asthma was associated with a specific haplotype of TSLP involving SNP rs1898671 (OR = 1.58, 95% CI: 1.10-2.27, p = 0.01). Association of this SNP with asthma was confirmed in an independent large population-based cohort consortium study (OR = 1.15, 95% CI: 1.07-1.23, p = 0.0003) and the results stratified by smoking status were also validated (ex-smokers: OR = 1.21, 95% CI: 1.08-1.34, p = 0.003; never-smokers: OR = 1.06, 95% CI: 0.94-1.17, p = 0.33).
CONCLUSIONS
Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.
背景
胸腺基质淋巴细胞生成素（TSLP）是一种由支气管上皮细胞产生的类白细胞介素 7 细胞因子，在哮喘中上调，并诱导树突状细胞成熟，支持 Th2 反应。环境污染物，包括烟草烟雾和柴油废气颗粒，上调 TSLP，表明 TSLP 可能是哮喘中环境污染物和免疫反应之间的接口。由于哮喘在城市社区中很普遍，TSLP 基因中的变异可能在这些人群的哮喘易感性中很重要。
目的
确定 TSLP 基因中的遗传变异是否与城市混合人群中的哮喘有关。
方法和主要结果
使用来自城市混合人群的 387 例临床诊断的哮喘病例和 212 例健康对照，分析了 TSLP 基因中的 10 个标签 SNP 与哮喘的关联。一个 SNP(rs1898671)在调整年龄、BMI、收入、教育和人群分层后，与哮喘呈显著关联（比值比（OR）=1.50；95%置信区间（95%CI）：1.09-2.05，p=0.01）。使用两种不同的方法调整人群分层，关联结果一致。按吸烟状况分层时，同一 SNP 显示与哮喘相关的风险显著增加，与前吸烟者（OR=2.00，95%CI：1.04-3.83，p=0.04）相关，但与从不吸烟者（OR=1.34；95%CI：0.93-1.94，p=0.11）无关。单体型特异性评分检验表明，与 TSLP 涉及 SNP rs1898671 的特定单体型相关的哮喘风险增加（OR=1.58，95%CI：1.10-2.27，p=0.01）。在一个独立的大型基于人群的队列联盟研究中（OR=1.15，95%CI：1.07-1.23，p=0.0003），证实了该 SNP 与哮喘的关联，并且按吸烟状况分层的结果也得到了验证（前吸烟者：OR=1.21，95%CI：1.08-1.34，p=0.003；从不吸烟者：OR=1.06，95%CI：0.94-1.17，p=0.33）。
结论
TSLP 基因中的遗传变异可能导致混合城市人群的哮喘易感性，存在基因与环境的相互作用。
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