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 & 1 others Joan Reibman

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article numbere25099
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 22 2011

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urban population
Urban Population
asthma
Asthma
odds ratio
confidence interval
Odds Ratio
Confidence Intervals
Single Nucleotide Polymorphism
Genes
Haplotypes
Population
Vehicle Emissions
Interleukin-7
Environmental Pollutants
haplotypes
Tobacco
thymic stromal lymphopoietin
Smoking
Smoke

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Liu, M., Rogers, L., Cheng, Q., Shao, Y., Fernandez-Beros, M. E., Hirschhorn, J. N., ... Reibman, J. (2011). Genetic variants of TSLP and asthma in an admixed urban population. PLoS One, 6(9), [e25099]. https://doi.org/10.1371/journal.pone.0025099

Genetic variants of TSLP and asthma in an admixed urban population. / Liu, Mengling; Rogers, Linda; Cheng, Qinyi; Shao, Yongzhao; Fernandez-Beros, Maria Elena; Hirschhorn, Joel N.; Lyon, Helen N.; Gajdos, Zofia K Z; Vedantam, Sailaja; Gregersen, Peter; Seldin, Michael F; Bleck, Bertram; Ramasamy, Adaikalavan; Hartikainen, Anna Liisa; Jarvelin, Marjo Riitta; Kuokkanen, Mikko; Laitinen, Tarja; Eriksson, Johan; Lehtimäki, Terho; Raitakari, Olli T.; Reibman, Joan.

In: PLoS One, Vol. 6, No. 9, e25099, 22.09.2011.

Research output: Contribution to journalArticle

Liu, M, Rogers, L, Cheng, Q, Shao, Y, Fernandez-Beros, ME, Hirschhorn, JN, Lyon, HN, Gajdos, ZKZ, 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 2011, 'Genetic variants of TSLP and asthma in an admixed urban population', PLoS One, vol. 6, no. 9, e25099. https://doi.org/10.1371/journal.pone.0025099
Liu M, Rogers L, Cheng Q, Shao Y, Fernandez-Beros ME, Hirschhorn JN et al. Genetic variants of TSLP and asthma in an admixed urban population. PLoS One. 2011 Sep 22;6(9). e25099. https://doi.org/10.1371/journal.pone.0025099
Liu, Mengling ; Rogers, Linda ; Cheng, Qinyi ; Shao, Yongzhao ; Fernandez-Beros, Maria Elena ; Hirschhorn, Joel N. ; Lyon, Helen N. ; Gajdos, Zofia K Z ; Vedantam, Sailaja ; Gregersen, Peter ; Seldin, Michael F ; Bleck, Bertram ; Ramasamy, Adaikalavan ; Hartikainen, Anna Liisa ; Jarvelin, Marjo Riitta ; Kuokkanen, Mikko ; Laitinen, Tarja ; Eriksson, Johan ; Lehtimäki, Terho ; Raitakari, Olli T. ; Reibman, Joan. / Genetic variants of TSLP and asthma in an admixed urban population. In: PLoS One. 2011 ; Vol. 6, No. 9.
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title = "Genetic variants of TSLP and asthma in an admixed urban population",
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.",
author = "Mengling Liu and Linda Rogers and Qinyi Cheng and Yongzhao Shao and Fernandez-Beros, {Maria Elena} and Hirschhorn, {Joel N.} and Lyon, {Helen N.} and Gajdos, {Zofia K Z} and Sailaja Vedantam and Peter Gregersen and Seldin, {Michael F} and Bertram Bleck and Adaikalavan Ramasamy and Hartikainen, {Anna Liisa} and Jarvelin, {Marjo Riitta} and Mikko Kuokkanen and Tarja Laitinen and Johan Eriksson and Terho Lehtim{\"a}ki and Raitakari, {Olli T.} and Joan Reibman",
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T1 - Genetic variants of TSLP and asthma in an admixed urban population

AU - Liu, Mengling

AU - Rogers, Linda

AU - Cheng, Qinyi

AU - Shao, Yongzhao

AU - Fernandez-Beros, Maria Elena

AU - Hirschhorn, Joel N.

AU - Lyon, Helen N.

AU - Gajdos, Zofia K Z

AU - Vedantam, Sailaja

AU - Gregersen, Peter

AU - Seldin, Michael F

AU - Bleck, Bertram

AU - Ramasamy, Adaikalavan

AU - Hartikainen, Anna Liisa

AU - Jarvelin, Marjo Riitta

AU - Kuokkanen, Mikko

AU - Laitinen, Tarja

AU - Eriksson, Johan

AU - Lehtimäki, Terho

AU - Raitakari, Olli T.

AU - Reibman, Joan

PY - 2011/9/22

Y1 - 2011/9/22

N2 - 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.

AB - 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.

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