Testing the possible negative association of type 1 diabetes and atopic disease by analysis of the interleukin 4 receptor gene.
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.
Maier
L M
LM
JDRF/WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Twells
R C J
RC
Howson
J M M
JM
Lam
A C
AC
Clayton
D G
DG
Smyth
D J
DJ
Savage
D
D
Carson
D
D
Patterson
C C
CC
Smink
L J
LJ
Walker
N M
NM
Burren
O S
OS
Nutland
S
S
Rance
H
H
Tuomilehto-Wolf
E
E
Tuomilehto
J
J
Guja
C
C
Ionescu-Tirgoviste
C
C
Undlien
D E
DE
Rønningen
K S
KS
Cucca
F
F
Todd
J A
JA
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
D006680:HLA Antigens; D019948:Receptors, Interleukin-4