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.
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, L; Guia, C; Ionescu Tirgoviste, C; Undlien, De; Ronningen, Ks; Cucca, Francesco; Todd, Ja. - In: GENES AND IMMUNITY. - ISSN 1466-4879. - 4:7(2003), pp. 469-475. [10.1038/sj.gene.6364007]
Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene
CUCCA, Francesco;
2003-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
