Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole blood and nasal epithelium

被引：13

作者：

Qi, Cancan ^{[1
,2
]}

Vonk, Judith M. ^{[2
,3
]}

van der Plaat, Diana A. ^{[2
,3
]}

Nieuwenhuis, Maartje A. E. ^{[2
]}

Dijk, F. Nicole ^{[1
,2
]}

Aissi, Dylan ^{[4
]}

Siroux, Valerie ^{[4
]}

Boezen, H. Marike ^{[2
,3
]}

Xu, Cheng-jian ^{[5
,6
,7
]}

Koppelman, Gerard H. ^{[1
,2
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Pulmonol & Pediat Allergy, Beatrix Childrens Hosp, POB 30-001, NL-9700 RB Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands

[4] Univ Grenoble Alpes, Team Environm Epidemiol Appl Reprod & Resp Hlth, IAB Inst Adv Biosci, Inserm,CNRS, F-38000 Grenoble, France

[5] Ctr Individualized Infect Med, Res Grp Bioinformat & Computat Genom, CiiM, Hannover, Germany

[6] Ctr Individualized Infect Med, Dept Gastroenterol Hepatol & Endocrinol, TWINCORE, Hannover, Germany

[7] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, Nijmegen, Netherlands

来源：

CLINICAL AND TRANSLATIONAL ALLERGY | 2020年 / 10卷 / 01期

关键词：

Asthma remission; DNA methylation; Whole blood; Nasal brushes; PEROXISOME PROLIFERATION; GENE; RISK; EXPRESSION; EXPOSURE; PACKAGE; TCF7L2;

D O I：

10.1186/s13601-020-00365-4

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission. Methods Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness. We analyzed differential DNA methylation of ClinR and ComR comparing to persistent asthma (PersA) in whole blood samples (n = 72) and nasal brushing samples (n = 97) in a longitudinal cohort of well characterized asthma patients. Significant findings of whole blood DNA methylation were tested for replication in two independent cohorts, Lifelines and Epidemiological study on the Genetics and Environment of Asthma (EGEA). Results We identified differentially methylated CpG sites associated with ClinR (7 CpG sites) and ComR (129 CpG sites) in whole blood. One CpG (cg13378519, Chr1) associated with ClinR was replicated and annotated to PEX11 (Peroxisomal Biogenesis Factor 11 Beta). The whole blood DNA methylation levels of this CpG were also different between ClinR and healthy subjects. One ComR-associated CpG (cg24788483, Chr10) that annotated to TCF7L2 (Transcription Factor 7 Like 2) was replicated and associated with expression of TCF7L2 gene. One out of seven ClinR-associated CpG sites and 8 out of 129 ComR-associated CpG sites identified from whole blood samples showed nominal significance (P < 0.05) and the same direction of effect in nasal brushes. Conclusion We identified DNA methylation markers possibly associated with clinical and complete asthma remission in nasal brushes and whole blood, and two CpG sites identified from whole blood can be replicated in independent cohorts and may play a role in peroxisome proliferation and Wnt signaling pathway.

引用

页数：13

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