title: The genetic variants of thymic stromal lymphopoietin protein in children with asthma and allergic rhinitis.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) is expressed by airway epithelial cells and plays a key role in immunological events in asthma. Data on the genetic variants of TSLP and its association with asthma and allergic rhinitis are scarce. We aimed to investigate the effects of the genetic variants of TSLP in children with asthma and allergic rhinitis.
  
  
  METHODS
  The genetic variants of the TSLP gene were determined by sequencing 25 asthmatic and 25 healthy children. In an association study, a population of 506 asthmatics and 157 healthy controls was screened for the following single-nucleotide polymorphisms (SNPs): rs3806933 and rs2289276 in the promoter region; rs11466741, rs11466742, and rs2289278 in intron 2; rs10073816, rs11466749, and rs11466750 in exon 4, and rs11466754 in 3'-UTR.
  
  
  RESULTS
  In Multifactor Dimensionality Reduction analysis, presence of the rs11466749 AA genotype with atopy was significantly associated with a diagnosis of asthma (testing set accuracy: 0.720 and cross validation: 9/10). Two functional SNPs showed a gender-specific association with allergy, i.e. the rs3806933 CC genotype with asthma in boys (p = 0.032, nonsignificant after multiple testing) and the rs2289276 CC genotype with higher eosinophil numbers in asthmatic girls (p = 0.003). The presence of allergic rhinitis in asthmatic children strengthened the association of the rs11466749 GG genotype with asthma (p = 0.001), and rs2289276 was significantly associated with lower FEV1 levels in asthmatics without allergic rhinitis (p = 0.003).
  
  
  CONCLUSIONS
  Variants in the gene encoding the TSLP protein may have differential effects on asthma phenotypes depending on gender, atopy, and the presence of allergic rhinitis.
authors: Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey.
authors: Esra
authors: E
authors: Birben
authors: Umit M
authors: UM
authors: Sahiner
authors: Cagatay
authors: C
authors: Karaaslan
authors: Tolga S
authors: TS
authors: Yavuz
authors: Erdal
authors: E
authors: Cosgun
authors: Omer
authors: O
authors: Kalayci
authors: Cansin
authors: C
authors: Sackesen
mesh_terms: D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics* / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin