Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene.
Maier LM., Twells RCJ., Howson JMM., Lam AC., Clayton DG., Smyth DJ., Savage D., Carson D., Patterson CC., Smink LJ., Walker NM., Burren OS., Nutland S., Rance H., Tuomilehto-Wolf E., Tuomilehto J., Guja C., Ionescu-Tirgoviste C., Undlien DE., Rønningen KS., Cucca F., Todd JA.
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.