title: Association of IL13 with total IgE: evidence against an inverse association of atopy and diabetes.
abstract: BACKGROUND
  Atopic illnesses, related to high circulating IgE levels, and the autoimmune disease type 1 diabetes, have been reported to be inversely associated. One possible explanation is that susceptibility alleles for one disease provide protection for the other.
  
  
  OBJECTIVE
  Using the largest sample sizes reported so far for the identification of genetic determinants of circulating IgE levels, we investigated associations between total serum IgE (log-transformed) and single nucleotide polymorphisms in 8 genes that are candidate susceptibility loci for IgE levels/atopic illness (IL13, IL4, IL4RA, FCER1B, IL12B, TBET) and/or type 1 diabetes (CTLA4, PTPN22, IL2RA).
  
  
  METHODS
  As many as 4570 DNA samples obtained from members of the British 1958 Birth Cohort were genotyped for 51 candidate variants, and the associations of alleles and genotypes with log-transformed serum IgE levels were evaluated by regression modeling.
  
  
  RESULTS
  We obtained evidence of association between IL13 variants and total serum IgE levels (P = .00002, explaining 0.59% of phenotypic variance). However, there was no evidence of association of the confirmed type 1 diabetes susceptibility genes CTLA4 and PTPN22 and the candidate gene IL2RA with IgE levels.
  
  
  CONCLUSIONS
  Allelic variation in the IL-13 gene is robustly confirmed as a contributor to the variance of IgE levels but has no detectable effect in type 1 diabetes.
  
  
  CONCLUSIONS
  Although the allelic variation at the confirmed IL-13 locus explains too little of the between-individual variation of circulating IgE to be of use for clinical prediction on its own, the discovery of additional susceptibility loci in the future may aid in the stratification of atopic subjects and improve risk assessment.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, UK. lisa.maier@cimr.cam.ac.uk
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Maier
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: Neil
authors.initials: N
authors.lastname: Walker
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Spickett
authors.forename: Richard W
authors.initials: RW
authors.lastname: Jones
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Wendy L
authors.initials: WL
authors.lastname: McArdle
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Lowe
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bailey
authors.forename: Felicity
authors.initials: F
authors.lastname: Payne
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood*; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D018793:Interleukin-13; D007073:Immunoglobulin E