New Insights Relating Gasdermin B to the Onset of Childhood Asthma.
New Insights Relating Gasdermin B to the Onset of Childhood Asthma.
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关于 Gasdermin B 与儿童哮喘发病的新见解。
DOI：
10.1165/rcmb.2022-0043ps
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发表时间：
2022
影响因子：
6.4
通讯作者：
Gern,JamesE
中科院分区：
文献类型：
--
作者：
Schoettler,Nathan;Dissanayake,Eishika;Craven,MarkW;Yee,JeremiahS;Eliason,Joshua;Schauberger,EricM;LemanskeJr,RobertF;Ober,Carole;Gern,JamesE
染色体 17q12-q21 是儿童期哮喘复制最多的基因位点。该基因座中包含约 10 个基因的多态性与家庭和户外的各种环境暴露相互作用，从而改变哮喘风险。然而，这些协会的功能基础及其与环境的联系仍然是个谜。在这个扩展区域内，气道上皮细胞中 GSDMB（gasdermin B）表达的调节已成为 17q12-q21 全基因组关联研究信号的主要机制。哮喘相关的 SNP 影响 GSDMB 转录物的丰度以及气道上皮细胞中 GSDMB 蛋白的功能特性。 GSDMB 是 Gasdermin 蛋白家族的成员，可调节细胞焦亡和对微生物感染的炎症反应。本综述的目的是综合最近关于 17q12-q21 SNP 与儿童哮喘关系的研究以及 GSDMB 基因表达或蛋白功能作为潜在机制的证据，并探讨 GSDMB 可能影响儿童期哮喘风险的潜在功能。
Chromosome 17q12-q21 is the most replicated genetic locus for childhood-onset asthma. Polymorphisms in this locus containing ∼10 genes interact with a variety of environmental exposures in the home and outdoors to modify asthma risk. However, the functional basis for these associations and their linkages to the environment have remained enigmatic. Within this extended region, regulation ofGSDMB(gasdermin B) expression in airway epithelial cells has emerged as the primary mechanism underlying the 17q12-q21 genome-wide association study signal. Asthma-associated SNPs influence the abundance ofGSDMBtranscripts as well as the functional properties of GSDMB protein in airway epithelial cells. GSDMB is a member of the gasdermin family of proteins, which regulate pyroptosis and inflammatory responses to microbial infections. The aims of this review are to synthesize recent studies on the relationship of 17q12-q21 SNPs to childhood asthma and the evidence pointing toGSDMBgene expression or protein function as the underlying mechanism and to explore the potential functions of GSDMB that may influence the risk of developing asthma during childhood.