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胎儿、婴儿和儿童时期 IgE 产生的不同遗传关联。

Different genetic associations of the IgE production among fetus, infancy and childhood.

机构信息

Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.

出版信息

PLoS One. 2013 Aug 1;8(8):e70362. doi: 10.1371/journal.pone.0070362. Print 2013.

Abstract

Elevation of serum IgE levels has long been associated with allergic diseases. Many genes have been linked to IgE production, but few have been linked to the developmental aspects of genetic association with IgE production. To clarify developmental genetic association, we investigated what genes and gene-gene interactions affect IgE levels among fetus, infancy and childhood in Taiwan individuals. A birth cohort of 571 children with completion of IgE measurements from newborn to 1.5, 3, and 6 years of age was subject to genetic association analysis on the 384-customized SNPs of 159 allergy candidate genes. Fifty-three SNPs in 37 genes on innate and adaptive immunity, and stress and response were associated with IgE production. Polymorphisms of the IL13, and the HLA-DPA1 and HLA-DQA1 were, respectively, the most significantly associated with the IgE production at newborn and 6 years of age. Analyses of gene-gene interactions indentified that the combination of NPSR1, rs324981 TT with FGF1, rs2282797 CC had the highest risk (85.7%) of IgE elevation at 1.5 years of age (P=1.46 × 10(-4)). The combination of IL13, CYFIP2 and PDE2A was significantly associated with IgE elevation at 3 years of age (P=5.98 × 10(-7)), and the combination of CLEC2D, COLEC11 and CCL2 was significantly associated with IgE elevation at 6 years of age (P=6.65 × 10(-7)). Our study showed that the genetic association profiles of the IgE production among fetus, infancy and childhood are different. Genetic markers for early prediction and prevention of allergic sensitization may rely on age-based genetic association profiles.

摘要

血清 IgE 水平升高与过敏疾病长期相关。许多基因与 IgE 产生有关,但与 IgE 产生的遗传关联的发育方面相关的基因很少。为了阐明发育遗传关联,我们研究了台湾个体中胎儿、婴儿和儿童期影响 IgE 水平的基因和基因-基因相互作用。对完成了从新生儿到 1.5、3 和 6 岁 IgE 测量的 571 名儿童进行了出生队列研究,对 159 个过敏候选基因的 384 个定制 SNP 进行了遗传关联分析。先天和适应性免疫、应激和反应中的 37 个基因的 53 个 SNP 与 IgE 产生有关。IL13、HLA-DPA1 和 HLA-DQA1 的多态性分别与新生儿和 6 岁时的 IgE 产生最显著相关。基因-基因相互作用分析确定,NPSR1、rs324981 TT 与 FGF1、rs2282797 CC 的组合在 1.5 岁时具有最高的 IgE 升高风险(85.7%)(P=1.46×10(-4))。IL13、CYFIP2 和 PDE2A 的组合与 3 岁时的 IgE 升高显著相关(P=5.98×10(-7)),CLEC2D、COLEC11 和 CCL2 的组合与 6 岁时的 IgE 升高显著相关(P=6.65×10(-7))。我们的研究表明,胎儿、婴儿和儿童期 IgE 产生的遗传关联谱不同。用于早期预测和预防过敏致敏的遗传标记可能依赖于基于年龄的遗传关联谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/274e/3731352/fa63143dad97/pone.0070362.g001.jpg

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