No evidence of association or interaction between the IL4RA, IL4, and IL13 genes in type 1 diabetes.
Attempts to identify susceptibility loci that, on their own, have marginal main effects by use of gene-gene interaction tests have increased in popularity. The results obtained from analyses of epistasis are, however, difficult to interpret. Gene-gene interaction, albeit only marginally significant, has recently been reported for the interleukin-4 and interleukin-13 genes (IL4 and IL13) with the interleukin-4 receptor A gene (IL4RA), contributing to the susceptibility of type 1 diabetes (T1D). We aimed to replicate these findings by genotyping both large family and case-control data sets and by using previously published data. Gene-gene interaction tests were performed using linear regression models in cases only. We did not find any single-locus associations with T1D and did not obtain evidence of gene-gene interaction. Additional support from independent samples will be even more important in the study of gene-gene interactions and other subgroup analyses.
Maier
Lisa M
LM
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom. lisa.maier@cimr.cam.ac.uk
Chapman
Juliet
J
Howson
Joanna M M
JM
Clayton
David G
DG
Pask
Rebecca
R
Strachan
David P
DP
McArdle
Wendy L
WL
Twells
Rebecca C J
RC
Todd
John A
JA
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*
D004268:DNA-Binding Proteins; C504000:IL4R protein, human; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D011956:Receptors, Cell Surface; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4