Terzikhan Natalie, Xu Hanfei, Edris Ahmed, Bracke Ken R, Verhamme Fien M, Stricker Bruno H C, Dupuis Josée, Lahousse Lies, O'Connor George T, Brusselle Guy G
Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Dept of Epidemiology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.
ERJ Open Res. 2021 Mar 15;7(1). doi: 10.1183/23120541.00567-2020. eCollection 2021 Jan.
Epigenetics may play an important role in the pathogenesis of lung diseases. However, little is known about the epigenetic factors that influence impaired gas exchange at the lung.
To identify the epigenetic signatures of the diffusing capacity of the lung measured by carbon monoxide uptake (the diffusing capacity of the lung for carbon monoxide ( )).
An epigenome-wide association study (EWAS) was performed on diffusing capacity, measured by carbon monoxide uptake ( ) and per alveolar volume ( ) (as / ), using the single-breath technique in 2674 individuals from two population-based cohort studies. These were the Rotterdam Study (RS, the "discovery panel") and the Framingham Heart Study (FHS, the "replication panel"). We assessed the clinical relevance of our findings by investigating the identified sites in whole blood and by lung tissue specific gene expression.
We identified and replicated two CpG sites (cg05575921 and cg05951221) that were significantly associated with / and one (cg05575921) suggestively associated with . Furthermore, we found a positive association between aryl hydrocarbon receptor repressor () gene (cg05575921) hypomethylation and gene expression of exocyst complex component 3 () in whole blood. We confirmed that the expression of in lung tissue is positively associated with / and .
We report on epigenome-wide associations with diffusing capacity in the general population. Our results suggest EXOC3 to be an excellent candidate, through which smoking-induced hypomethylation of might affect pulmonary gas exchange.
表观遗传学可能在肺部疾病的发病机制中起重要作用。然而，关于影响肺部气体交换受损的表观遗传因素知之甚少。
确定通过一氧化碳摄取量测量的肺弥散能力（肺一氧化碳弥散量（ ））的表观遗传特征。
在两项基于人群的队列研究的2674名个体中，采用单呼吸技术，对通过一氧化碳摄取量（ ）和每肺泡容积（ ）（以 / 表示）测量的弥散能力进行全表观基因组关联研究（EWAS）。这两项研究分别是鹿特丹研究（RS，“发现组”）和弗雷明汉心脏研究（FHS，“复制组”）。我们通过研究全血中鉴定出的位点以及肺组织特异性基因表达来评估我们研究结果的临床相关性。
我们鉴定并重复验证了两个与 / 显著相关的CpG位点（cg05575921和cg05951221），以及一个与 可能相关联的位点（cg05575921）。此外，我们发现全血中芳烃受体阻遏物（ ）基因（cg05575921）低甲基化与外泌体复合体成分3（ ）的基因表达呈正相关。我们证实 在肺组织中的表达与 / 以及 呈正相关。
我们报告了普通人群中全表观基因组与弥散能力的关联。我们的结果表明EXOC3是一个很好的候选基因，吸烟诱导的 低甲基化可能通过它影响肺气体交换。
