Genetic variants of TSLP and asthma in an admixed urban population

Mengling Liu, Linda Rogers, Qinyi Cheng, Yongzhao Shao, Maria Elena Fernandez-Beros, Joel N Hirschhorn, Helen N Lyon, Zofia K Z Gajdos, Sailaja Vedantam, Peter Gregersen, Michael F Seldin, Bertram Bleck, Adaikalavan Ramasamy, Anna-Liisa Hartikainen, Marjo-Riitta Jarvelin, Mikko Kuokkanen, Tarja Laitinen, Johan Eriksson, Terho Lehtimäki, Olli T Raitakari, Joan Reibman, Mengling Liu, Linda Rogers, Qinyi Cheng, Yongzhao Shao, Maria Elena Fernandez-Beros, Joel N Hirschhorn, Helen N Lyon, Zofia K Z Gajdos, Sailaja Vedantam, Peter Gregersen, Michael F Seldin, Bertram Bleck, Adaikalavan Ramasamy, Anna-Liisa Hartikainen, Marjo-Riitta Jarvelin, Mikko Kuokkanen, Tarja Laitinen, Johan Eriksson, Terho Lehtimäki, Olli T Raitakari, Joan Reibman

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00212537.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Scatter-plot of the first and…
Figure 1. Scatter-plot of the first and second principal components.
Scatter-plot of the first and second principal components calculated from the genotypes of 213 AIMs. The first principal component scores showed good separation between the self-reported non-Hispanic white and self-reported non-Hispanic black groups, while the principal component scores of self-reported Hispanic group were in-between.

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