白细胞介素 13 基因多态性与特应性皮炎的关联：精细定位和单倍型分析。

Association of IL13 genetic polymorphisms with atopic dermatitis: Fine mapping and haplotype analysis.

机构信息

Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea.

Department of Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Ann Allergy Asthma Immunol. 2020 Sep;125(3):287-293. doi: 10.1016/j.anai.2020.04.023. Epub 2020 May 1.

DOI:10.1016/j.anai.2020.04.023

PMID:32371243

Abstract

BACKGROUND

Although previous studies had reported an important role of interleukin 13 (IL13) and its genetic polymorphisms in atopic dermatitis (AD), many of these previous reports focused on the missense variant rs20541 (Gln144Arg) without fine mapping of the gene region.

OBJECTIVE

To analyze the potential associations of other IL13 variants and their haplotypes with AD and assess total serum immunoglobulin E (IgE) levels.

METHODS

We performed fine mapping of single-nucleotide polymorphisms (SNPs) within the IL13 gene in a pilot study of 495 children with AD and 444 healthy controls. Then, we conducted a replication study of 757 children with AD and 1620 healthy controls to evaluate the association between the rs20541 variant of IL13 and AD.

RESULTS

In the pilot study, the rs20541 and rs1295685 SNPs in the 3'-untranslated region of IL13 had significant associations with AD (P < .001 and .01, respectively). In addition, 2 haplotypes (BL2_ht1 and BL2_ht2), which harbored the significant rs20541 and rs1295685 SNPs, had an association with AD (minimum P = .006). BL2_ht1 and BL2_ht2 had nominal signals associated with the total serum IgE levels (P < .05) but not with the severity of AD (P > .05). In the replication study, rs20541 was associated with the total serum IgE levels but not with the severity of AD.

CONCLUSION

An additional IL13 gene SNP, rs1295685, has a strong linkage disequilibrium with rs20541, and its haplotypes are associated with AD and the total serum IgE levels.

摘要

背景

虽然之前的研究已经报道了白细胞介素 13（IL13）及其遗传多态性在特应性皮炎（AD）中的重要作用，但这些之前的研究报告大多集中在错义变异 rs20541（Gln144Arg）上，而没有对基因区域进行精细定位。

目的

分析 IL13 其他变体及其单倍型与 AD 的潜在关联，并评估总血清免疫球蛋白 E（IgE）水平。

方法

我们对 495 名 AD 患儿和 444 名健康对照者进行了 IL13 基因内单核苷酸多态性（SNP）的精细定位研究。然后，我们对 757 名 AD 患儿和 1620 名健康对照者进行了复制研究，以评估 IL13 中 rs20541 变异与 AD 之间的关联。

结果

在初步研究中，IL13 3'-非翻译区的 rs20541 和 rs1295685 SNP 与 AD 具有显著关联（P<.001 和.01，分别）。此外，携带有显著 rs20541 和 rs1295685 SNP 的 2 个单倍型（BL2_ht1 和 BL2_ht2）与 AD 相关（最小 P<.006）。BL2_ht1 和 BL2_ht2 与总血清 IgE 水平具有名义关联（P<.05），但与 AD 的严重程度无关（P>.05）。在复制研究中，rs20541 与总血清 IgE 水平相关，但与 AD 的严重程度无关。