title: Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene.
abstract: Variations in the interleukin 4 receptor A (IL4RA) gene have been reported to be associated with atopy, asthma, and allergy, which may occur less frequently in subjects with type 1 diabetes (T1D). Since atopy shows a humoral immune reactivity pattern, and T1D results from a cellular (T lymphocyte) response, we hypothesised that alleles predisposing to atopy could be protective for T1D and transmitted less often than the expected 50% from heterozygous parents to offspring with T1D. We genotyped seven exonic single nucleotide polymorphisms (SNPs) and the -3223 C>T SNP in the putative promoter region of IL4RA in up to 3475 T1D families, including 1244 Finnish T1D families. Only the -3223 C>T SNP showed evidence of negative association (P=0.014). There was some evidence for an interaction between -3233 C>T and the T1D locus IDDM2 in the insulin gene region (P=0.001 in the combined and P=0.02 in the Finnish data set). We, therefore, cannot rule out a genetic effect of IL4RA in T1D, but it is not a major one.
authors.affiliation: JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Maier
authors.forename: R C J
authors.initials: RC
authors.lastname: Twells
authors.forename: J M M
authors.initials: JM
authors.lastname: Howson
authors.forename: A C
authors.initials: AC
authors.lastname: Lam
authors.forename: D G
authors.initials: DG
authors.lastname: Clayton
authors.forename: D J
authors.initials: DJ
authors.lastname: Smyth
authors.forename: D
authors.initials: D
authors.lastname: Savage
authors.forename: D
authors.initials: D
authors.lastname: Carson
authors.forename: C C
authors.initials: CC
authors.lastname: Patterson
authors.forename: L J
authors.initials: LJ
authors.lastname: Smink
authors.forename: N M
authors.initials: NM
authors.lastname: Walker
authors.forename: O S
authors.initials: OS
authors.lastname: Burren
authors.forename: S
authors.initials: S
authors.lastname: Nutland
authors.forename: H
authors.initials: H
authors.lastname: Rance
authors.forename: E
authors.initials: E
authors.lastname: Tuomilehto-Wolf
authors.forename: J
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: C
authors.initials: C
authors.lastname: Guja
authors.forename: C
authors.initials: C
authors.lastname: Ionescu-Tirgoviste
authors.forename: D E
authors.initials: DE
authors.lastname: Undlien
authors.forename: K S
authors.initials: KS
authors.lastname: Rønningen
authors.forename: F
authors.initials: F
authors.lastname: Cucca
authors.forename: J A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002885:Chromosomes, Human, Pair 16; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005091:Exons; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D044465:White People
chemical_list: D006680:HLA Antigens; D019948:Receptors, Interleukin-4