title: Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetes.
abstract: BACKGROUND
  The genetic basis of the autoimmune disease type 1 diabetes (T1D) has now been largely determined, so now we can compare these findings with emerging genetic knowledge of disorders and phenotypes that have been negatively or positively associated with T1D historically. Here, we assessed the role in T1D of variants previously reported to be associated with atopic diseases and epithelial barrier function, profilaggrin (FLG), and those that affect the expression levels of the proinflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)γ and IL-18.
  
  
  METHODS
  We genotyped single nucleotide polymorphisms (SNPs): -105/rs28665122 in SELS or SEPS1 (selenoprotein), three single nucleotide polymorphisms in IL18 (-105/rs360717, +183/rs5744292 and +1467/rs574456) and R501X/rs61816761 in FLG, the major locus associated with atopic dermatitis and predisposing to asthma, in a minimum of 6743 T1D cases and 7864 controls.
  
  
  RESULTS
  No evidence of T1D association was found for any of the SNPs we genotyped at FLG, SELS or IL18 (p≥0.03), nor with haplotypes of IL18 (p=0.82). Review of previous T1D genome-wide association results revealed that four (human leucocyte antigen (HLA), gasdermin B/ORM1 (Saccharomyces cerevisiae)-like/gasdermin B/, GSDMB/ORMDL3/GSDMA and IL2RB) of ten loci recently reported to be associated with asthma were associated with T1D (p≤0.005).
  
  
  CONCLUSIONS
  These results show that there are shared genetic associations for atopy-related traits and T1D, and this might help in the future to understand the mechanisms, pathways and environmental factors that underpin the rapid rise in incidence of both disorders in children.
authors: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0XY, UK.
authors: Nada M
authors: NM
authors: Saleh
authors: Srilakshmi M
authors: SM
authors: Raj
authors: Deborah J
authors: DJ
authors: Smyth
authors: Chris
authors: C
authors: Wallace
authors: Joanna M M
authors: JM
authors: Howson
authors: Louise
authors: L
authors: Bell
authors: Neil M
authors: NM
authors: Walker
authors: Helen E
authors: HE
authors: Stevens
authors: John A
authors: JA
authors: Todd
mesh_terms: D001249:Asthma / Q000235:genetics; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051140:Selenoproteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D020382:Interleukin-18; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma