Genetic variants of TSLP and asthma in an admixed urban population.
Genetic variants of TSLP and asthma in an admixed urban population.
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TSLP和哮喘的遗传变异在混合城市人口中。
DOI：
10.1371/journal.pone.0025099
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Reibman J
中科院分区：
文献类型：
--
作者：
Liu M;Rogers L;Cheng Q;Shao Y;Fernandez-Beros ME;Hirschhorn JN;Lyon HN;Gajdos ZK;Vedantam S;Gregersen P;Seldin MF;Bleck B;Ramasamy A;Hartikainen AL;Jarvelin MR;Kuokkanen M;Laitinen T;Eriksson J;Lehtimäki T;Raitakari OT;Reibman J
胸腺基质淋巴生成素(TSLP)是一种由支气管上皮细胞产生的IL7样细胞因子，在哮喘中上调，并诱导树突状细胞成熟，支持Th2反应。包括烟草烟雾和柴油废气颗粒在内的环境污染物可上调TSLP，提示TSLP可能是环境污染和哮喘免疫反应之间的界面。由于哮喘在城市社区中普遍存在，TSLP基因的变异可能在这些人群的哮喘易感性中起重要作用。确定TSLP的基因变异是否与城市混合人群中的哮喘有关。来自城市混合人群的387例临床诊断为哮喘患者和212例健康对照，分析了TSLP基因中的10个Tag-SNPs与哮喘的相关性。在调整了年龄、体重指数、收入、教育程度和人口分层后，1个单核苷酸多态(Rs1898671)在名义上与哮喘显著相关(优势比(OR) = 1.5 0；95%可信区间(95%CI)：1.0 9-2.0 5，p = 0.0 1)。使用两种不同的方法对人口分层进行调整，关联结果是一致的。当按吸烟状况分层时，同一单核苷酸多态在戒烟者中显著增加与哮喘相关的风险(OR = 2.0 0，95%CI：1.0 4~3.83，p = 0.0 4)，而在从不吸烟者中并不显著(OR = 1.3 4；95%CI：0.93~1.94，p = 0.11)。单倍型特异性计分检验显示，携带rs1898671单核苷酸多态的TSLP个体患哮喘的风险增加(OR = 1.58，95%CI：1.10~2.27，p = 0.01)。这一单核苷酸多态与哮喘的关联已在一项独立的大型人群队列研究中得到证实(OR = 1.15，95%CI：1.07-1.23，p = 0.0003)，并验证了按吸烟状况分层的结果(有吸烟者：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)。TSLP基因变异可能与混合的城市人群哮喘易感性有关，这与基因和环境的交互作用有关。
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. To determine whether genetic variants in TSLP are associated with asthma in an urban admixed population. 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). Genetic variants in TSLP may contribute to asthma susceptibility in admixed urban populations with a gene and environment interaction.
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影响因子：
3.9
作者：
Kosoy, Roman;Nassir, Rami;Tian, Chao;White, Phoebe A.;Butler, Lesley M.;Silva, Gabriel;Kittles, Rick;Alarcon-Riquelme, Marta E.;Gregersen, Peter K.;Belmont, John W.;De La Vega, Francisco M.;Seldin, Michael F.
通讯作者：
Seldin, Michael F.
DOI：
10.1186/1710-1492-6-4
发表时间：
2010-03-15
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
Nguyen KD;Vanichsarn C;Nadeau KC
通讯作者：
Nadeau KC
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
4.4
作者：
Reche, PA;Soumelis, V;Bazan, JF
通讯作者：
Bazan, JF
DOI：
10.1164/rccm.200711-1697oc
发表时间：
2008-04-15
影响因子：
24.7
作者：
Hunninghake, Gary M.;Lasky-Su, Jessica;Celedon, Juan C.
通讯作者：
Celedon, Juan C.