Association of IL 13 with total IgE:: Evidence against an inverse association of atopy and diabetes
Association of IL 13 with total IgE:: Evidence against an inverse association of atopy and diabetes
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DOI：
10.1016/j.jaci.2005.12.1354
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发表时间：
2006-06-01
影响因子：
14.2
通讯作者：
Strachan, David P.
中科院分区：
文献类型：
--
作者：
Maier, Lisa M.;Howson, Joanna M. M.;Strachan, David P.
背景资料：据报道，与高循环IgE水平相关的特应性疾病和自身免疫性疾病1型糖尿病呈负相关。一种可能的解释是，一种疾病的易感等位基因为另一种疾病提供了保护。目的：使用迄今为止报道的最大样本量来鉴定循环IgE水平的遗传决定因素，我们研究了血清总IgE与血清总IgE水平之间的关系。IgE水平/特应性疾病的候选易感基因8个基因的（对数转换）和单核苷酸多态性（IL 13、IL 4、IL 4 RA、FCER 1B、IL 12 B、TBET）和/或1型糖尿病（CTLA4、PTPN22、IL2RA）。从英国1958年出生队列的成员中获得的多达4570个DNA样本被基因分型为51个候选变体，用回归模型分析等位基因和基因型与对数转换后血清IgE水平的关系。我们获得了IL 13变异体和血清总IgE水平之间相关性的证据（P = 0.00002，解释了0.59%的表型方差）。然而，有没有证据表明关联的确认1型糖尿病的易感基因CTLA 4和PTPN 22和候选基因IL 2 RA与IgE levels.Conclusion：IL-13基因的等位基因变异被有力地证实为一个贡献者的IgE水平的变化，但在1型糖尿病中没有检测到的效果。临床意义：尽管IL-13基因座的等位基因变异对循环IgE个体间变异的解释太少，无法单独用于临床预测，但未来发现其他易感基因座可能有助于特应性受试者的分层，并改善风险评估。
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.