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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Mengling
authors.initials: M
authors.lastname: Liu
authors.forename: Linda
authors.initials: L
authors.lastname: Rogers
authors.forename: Qinyi
authors.initials: Q
authors.lastname: Cheng
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Shao
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Fernandez-Beros
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Helen N
authors.initials: HN
authors.lastname: Lyon
authors.forename: Zofia K Z
authors.initials: ZK
authors.lastname: Gajdos
authors.forename: Sailaja
authors.initials: S
authors.lastname: Vedantam
authors.forename: Peter
authors.initials: P
authors.lastname: Gregersen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Bertram
authors.initials: B
authors.lastname: Bleck
authors.forename: Adaikalavan
authors.initials: A
authors.lastname: Ramasamy
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.forename: Mikko
authors.initials: M
authors.lastname: Kuokkanen
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
authors.forename: Johan
authors.initials: J
authors.lastname: Eriksson
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.forename: Joan
authors.initials: J
authors.lastname: Reibman
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014505:Urban Population; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin