title: An inverse association between history of childhood eczema and subsequent risk of type 1 diabetes that is not likely to be explained by HLA-DQ, PTPN22, or CTLA4 polymorphisms.
abstract: BACKGROUND
  Established genetic susceptibility loci for type 1 diabetes are important in immune regulation and may play a role also in atopic disorders, potentially explaining the inverse association between childhood eczema and subsequent risk for type 1 diabetes previously reported.
  
  
  OBJECTIVE
  We aimed to directly assess whether HLA-DQ, CTLA4, and PTPN22 genes could explain the putative association between childhood eczema and lower subsequent risk of type 1 diabetes observed in several case-control studies.
  
  
  METHODS
  We designed a case-control study with 339 incident cases of type 1 diabetes identified in the Norwegian childhood diabetes registry, and 985 population-based control children. DNA was collected, and physician-diagnosed childhood eczema was ascertained by a questionnaire administered to the parents of children with and without type 1 diabetes.
  
  
  RESULTS
  The previously reported association between childhood eczema and lower risk of type 1 diabetes was confirmed (odds ratio,OR, 0.61, 95% confidence interval, CI, 0.40-0.95] and this was consistent in subgroups defined by HLA-DQ, CTLA4, and PTPN22 genotypes. The OR was essentially not influenced by adjustment for genetic variation at these loci (OR simultaneously adjusted for the three genetic loci: 0.55, 95% CI: 0.32-0.92). The ratio of the unadjusted to adjusted OR was 1.12, with a corresponding 95% CI from 0.84 to 1.50.
  
  
  CONCLUSIONS
  In this first study of its kind, we demonstrated directly that the observed inverse association between childhood eczema and type 1 diabetes is not likely to be explained by the established diabetes susceptibility genes HLA-DQ, CTLA4, or PTPN22.
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, NO-0403 Oslo, Norway. lars.christian.stene@fhi.no
authors.forename: Lars C
authors.initials: LC
authors.lastname: Stene
authors.forename: Kjersti S
authors.initials: KS
authors.lastname: Rønningen
authors.forename: Marit
authors.initials: M
authors.lastname: Bjørnvold
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
authors.forename: Geir
authors.initials: G
authors.lastname: Joner
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics* / Q000276:immunology; D004485:Eczema / Q000150:complications* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22