Diabetes
J
Allergy Clin Immunol.
2006 Jun;117(6):1306-13. Epub
2006 Apr 3.
Association of IL13 with total IgE: Evidence against an inverse association of atopy and diabetes.
Maier
LM, Howson JM, Walker
N, Spickett GP, Jones
RW, Ring
SM, McArdle WL, Lowe
CE, Bailey
R, Payne
F, Todd
JA, Strachan DP.
From the Juvenile Diabetes Research Foundation/Wellcome
Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical
Research, University of
BACKGROUND: Atopic illnesses, related to high
circulating IgE levels, and the autoimmune
disease type 1 diabetes, have been reported to be
inversely associated. One possible explanation is that susceptibility
alleles for one disease provide protection for the other. OBJECTIVE: Using
the largest sample sizes reported so far for the identification of genetic
determinants of circulating IgE levels, we
investigated associations between total serum IgE
(log-transformed) and single nucleotide polymorphisms in 8 genes that are
candidate susceptibility loci for IgE levels/atopic illness (IL13, IL4, IL4RA, FCER1B, IL12B, TBET)
and/or type 1 diabetes (CTLA4, PTPN22, IL2RA). METHODS: As many as 4570 DNA
samples obtained from members of the British 1958 Birth Cohort were
genotyped for 51 candidate variants, and the
associations of alleles and genotypes with log-transformed serum IgE levels were evaluated by regression modeling.
RESULTS: We obtained evidence of association between IL13 variants and
total serum IgE levels (P = .00002, explaining
0.59% of phenotypic variance). However, there was no evidence of
association of the confirmed type 1 diabetes susceptibility genes CTLA4 and
PTPN22 and the candidate gene IL2RA with IgE
levels. CONCLUSION: Allelic variation in the IL-13 gene is robustly
confirmed as a contributor to the variance of IgE
levels but has no detectable effect in type 1 diabetes. CLINICAL
IMPLICATIONS: Although the allelic variation at the confirmed IL-13 locus
explains too little of the between-individual variation of circulating IgE to be of use for clinical prediction on its own,
the discovery of additional susceptibility loci in the future may aid in
the stratification of atopic subjects and improve
risk assessment.
PMID: 16750991 [PubMed - in process]