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哮喘和鼻炎中的DNA甲基化生物标志物:我们做到了吗?

DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

作者信息

Legaki Evangelia, Arsenis Christos, Taka Styliani, Papadopoulos Nikolaos G

机构信息

Allergy and Clinical Immunology Unit, Second Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Clin Transl Allergy. 2022 Mar;12(3):e12131. doi: 10.1002/clt2.12131.

Abstract

The study of epigenetics has improved our understanding of mechanisms underpinning gene-environment interactions and is providing new insights in the pathophysiology of respiratory allergic diseases. We reviewed the literature on DNA methylation patterns across different tissues in asthma and/or rhinitis and attempted to elucidate differentially methylated loci that could be used to characterize asthma or rhinitis. Although nasal and bronchial epithelia are similar in their histological structure and cellular composition, genetic and epigenetic regulation may differ across tissues. Advanced methods have enabled comprehensive, high-throughput methylation profiling of different tissues (bronchial or nasal epithelial cells, whole blood or isolated mononuclear cells), in subjects with respiratory conditions, aiming to elucidate gene regulation mechanisms and identify new biomarkers. Several genes and CpGs have been suggested as asthma biomarkers, though research on allergic rhinitis is still lacking. The most common differentially methylated loci presented in both blood and nasal samples are ACOT7, EPX, KCNH2, SIGLEC8, TNIK, FOXP1, ATPAF2, ZNF862, ADORA3, ARID3A, IL5RA, METRNL and ZFPM1. Overall, there is substantial variation among studies, (i.e. sample sizes, age groups and disease phenotype). Greater variability of analysis method detailed phenotypic characterization and age stratification should be taken into account in future studies.

摘要

表观遗传学的研究增进了我们对基因-环境相互作用机制的理解,并为呼吸道过敏性疾病的病理生理学提供了新的见解。我们回顾了关于哮喘和/或鼻炎不同组织中DNA甲基化模式的文献,并试图阐明可用于表征哮喘或鼻炎的差异甲基化位点。尽管鼻和支气管上皮在组织结构和细胞组成上相似,但不同组织的遗传和表观遗传调控可能存在差异。先进的方法能够对患有呼吸道疾病的受试者的不同组织(支气管或鼻上皮细胞、全血或分离的单核细胞)进行全面、高通量的甲基化分析,旨在阐明基因调控机制并识别新的生物标志物。虽然关于变应性鼻炎的研究仍然缺乏,但已有多个基因和CpG被认为是哮喘的生物标志物。血液和鼻样本中最常见的差异甲基化位点是ACOT7、EPX、KCNH2、SIGLEC8、TNIK、FOXP1、ATPAF2、ZNF862、ADORA3、ARID3A、IL5RA、METRNL和ZFPM1。总体而言,各研究之间存在很大差异(即样本量、年龄组和疾病表型)。未来的研究应考虑分析方法、详细表型特征和年龄分层方面更大的变异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c56d/8967268/3f8a0d928cb6/CLT2-12-e12131-g002.jpg

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