Mendoza Nuria, Rivas Eva, Rodriguez-Roisin Roberto, Garcia Tamara, Bruguera Miquel, Agusti Alvar, Faner Rosa
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
PLoS One. 2021 Feb 25;16(2):e0245046. doi: 10.1371/journal.pone.0245046. eCollection 2021.
The hepatopulmonary syndrome (HPS) is defined by the presence of pulmonary gas exchange abnormalities due to intrapulmonary vascular dilatations in patients with chronic liver disease. Changes in DNA methylation reflect the genomic variation. Since liver transplant (LT) reverts HPS we hypothesized that it may be associated with specific liver epigenetic changes. Thus, the aim of this study was to investigate the role of the liver epigenome in patients with HPS. We extracted DNA from paraffin embedded liver tissue samples from 10 patients with HPS and 10 age-, sex- and MELD (Model for End-stage Liver Disease)-matched controls. DNA methylation was determined using the 850K array (Illumina). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules related to defining physiologic characteristics of HPS. Only 12 out of the 20 liver biopsies (7 HPS and 5 controls) had sufficient quality to be analyzed. None of the 802,688 DNA probes analyzed in the case control comparison achieved a significant False Discovery Rate (FDR). WGCNA identified 5 co-methylated gene-modules associated to HPS markers, mainly related to nervous and neuroendocrine system, apoptotic processes, gut bacterial translocation, angiogenesis and vascular remodeling ontologies. To conclude, HPS is associated with nervous/neuroendocrine system and vascular remodeling related liver epigenetic changes.
肝肺综合征（HPS）定义为慢性肝病患者因肺内血管扩张导致的肺气体交换异常。DNA甲基化变化反映基因组变异。由于肝移植（LT）可逆转HPS，我们推测它可能与特定的肝脏表观遗传变化有关。因此，本研究的目的是探讨肝脏表观基因组在HPS患者中的作用。我们从10例HPS患者以及10例年龄、性别和终末期肝病模型（MELD）相匹配的对照的石蜡包埋肝组织样本中提取DNA。使用850K芯片（Illumina）测定DNA甲基化。加权基因共表达网络分析（WGCNA）用于识别与定义HPS生理特征相关的模块。20例肝活检样本中只有12例（7例HPS和5例对照）质量足够用于分析。病例对照比较中分析的802,688个DNA探针均未达到显著的错误发现率（FDR）。WGCNA识别出5个与HPS标志物相关的共甲基化基因模块，主要与神经和神经内分泌系统、凋亡过程、肠道细菌易位、血管生成和血管重塑本体相关。总之，HPS与神经/神经内分泌系统以及血管重塑相关的肝脏表观遗传变化有关。
