Association of IL13 with total IgE: evidence against an inverse association of atopy and diabetes.

Journal of Allergy and Clinical Immunology

PubMedID: 16750991

Maier LM, Howson JM, Walker N, Spickett GP, Jones RW, Ring SM, McArdle WL, Lowe CE, Bailey R, Payne F, Todd JA, Strachan DP. Association of IL13 with total IgE: evidence against an inverse association of atopy and diabetes. J Allergy Clin Immunol. 2006;117(6):1306-13.
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.