title: Polymorphisms in eosinophil pathway genes, asthma and atopy.
abstract: BACKGROUND
  Eosinophilic inflammation is considered to play an important role in the development as well as in the perpetuation of asthma. As eosinophil production and survival is under genetic control we investigated whether polymorphisms in eosinophil regulation pathway genes (IL-3, IL-5, GM-CSF and their respective enhancers and receptors) may influence the development of atopic diseases.
  
  
  METHODS
  In two large study populations of children, the German part of the International Study of Asthma and Allergy in Childhood (ISAAC II) and the German Multicentre Atopy Study (MAS), 3099 and 824 children, seven polymorphisms previously associated with the development of atopic diseases were genotyped: two in and around the GM-CSF gene (Ile117Thr and T3085G), one in IL-3 (Pro27Ser), in IL-5 (C-746T), and in the IL-5 high affinity receptor chain IL-5R (G-80A) and two in the common receptor chain CSFR2b for IL-3, IL-5, and GM-CSF (Asp312Asn and Glu249Gln). Statistical analyses were performed using chi-squared tests and variance analyses. Gene by gene interactions were evaluated in logistic regression models.
  
  
  RESULTS
  The T allele at position -746 in the IL-5 gene was significantly protective for atopy in the ISAAC II population (P = 0.006). Furthermore, the risk for atopic asthma was decreased in carriers of the T allele (P = 0.036) and evidence for interaction with the enhancer polymorphism 3085 bp 3' of GM-CSF was detected.
  
  
  CONCLUSIONS
  IL-5 C-746T influenced atopic outcomes and showed evidence for gene by gene interaction. No significant associations were found with all other tested polymorphisms in the eosinophil regulation pathway after correction for multiple testing.
authors.affiliation: University Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kabesch
authors.forename: M
authors.initials: M
authors.lastname: Depner
authors.forename: I
authors.initials: I
authors.lastname: Dahmen
authors.forename: S K
authors.initials: SK
authors.lastname: Weiland
authors.forename: C
authors.initials: C
authors.lastname: Vogelberg
authors.forename: B
authors.initials: B
authors.lastname: Niggemann
authors.forename: S
authors.initials: S
authors.lastname: Lau
authors.forename: T
authors.initials: T
authors.lastname: Illig
authors.forename: N
authors.initials: N
authors.lastname: Klopp
authors.forename: U
authors.initials: U
authors.lastname: Wahn
authors.forename: D
authors.initials: D
authors.lastname: Reinhardt
authors.forename: E
authors.initials: E
authors.lastname: von Mutius
authors.forename: R
authors.initials: R
authors.lastname: Nickel
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000276:immunology; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D015848:Interleukin-5 / Q000235:genetics; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D012882:Skin Tests; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: D015848:Interleukin-5; D007073:Immunoglobulin E; D012965:Sodium Chloride; D006632:Histamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor