人肺组织中的DNA甲基化分析识别与慢性阻塞性肺疾病相关的基因
2016/10/09
摘要
慢性阻塞性肺疾病（COPD）是一种以遗传和表型异质性为特征的吸烟相关疾病。虽然相关关系研究已经确定了多个基因区域重复与慢性阻塞性肺病相关，遗传变异只部分解释了肺部疾病的易感性，并提出了表观遗传的相关性。我们从46个肺功能正常的对照受试者和114例COPD患者的肺组织匀浆样品中进行了全基因组DNA甲基化分析，所有的受试者均为吸烟者。差异甲基化位点与以前的全基因组关联研究结果进行了整合。从前535个差异甲基化位点中，在病例和对照之间筛选一个5%最小平均差异的甲基化，有丰富的CpG 岛。通路分析显示具有丰富的转录因子。前几个与以前的GWAS交叉的差异显著的甲基化位点为 CHRM1，GLT1D1，和C10orf11；通过GWAS p值排序，前面的位点包括FRMD4A, THSD4, 和C10orf11。表观遗传关联研究补充遗传关联研究，以确定潜在参与慢性阻塞性肺病发病机制的基因。牵连在哮喘和肺功能的基因和转录因子的富集表明，可通过差异甲基化和与更广泛的GWAS交叉来识别潜在的致病相关基因。
关键词：DNA甲基化分析；慢性阻塞性肺疾病；表观遗传学
（杨冬 审校）
Epigenetics. 2016 Aug 26:0. [Epub ahead of print]
DNA methylation profiling in human lung tissue identifies genes associated with COPD.
Morrow JD1, Cho MH1,2, Hersh CP1,2, Pinto-Plata V3, Celli B2, Marchetti N4, Criner G4, Bueno R5, Washko G2, Glass K1, Choi AM6, Quackenbush J7,Silverman EK1,2, DeMeo DL1,2.
Author information
Abstract
Chronic obstructive pulmonary disease (COPD) is a smoking-related disease characterized by genetic and phenotypic heterogeneity. Although association studies have identified multiple genomic regions with replicated associations to COPD, genetic variation only partially explains the susceptibility to lung disease, and suggests the relevance of epigenetic investigations. We performed genome-wide DNA methylation profiling in homogenized lung tissue samples from 46 control subjects with normal lung function and 114 subjects with COPD, all former smokers. The differentially methylated loci were integrated with previous genome-wide association study results. The top 535 differentially methylated sites, filtered for a minimum mean methylation difference of 5% between cases and controls, were enriched for CpG shelves and shores. Pathway analysis revealed enrichment for transcription factors. The top differentially methylated sites from the intersection with previous GWAS were in CHRM1, GLT1D1, and C10orf11; sorted by GWAS P-value, the top sites included FRMD4A, THSD4, and C10orf11. Epigenetic association studies complement genetic association studies to identify genes potentially involved in COPD pathogenesis. Enrichment for genes implicated in asthmaand lung function and for transcription factors suggests the potential pathogenic relevance of genes identified through differential methylation and the intersection with a broader range of GWAS associations.
KEYWORDS:DNA methylation profiling; chronic obstructive pulmonary disease; epigenetics
Epigenetics. 2016 Aug 26:0. [Epub ahead of print]
上一篇：
一个PAI-1基因多态性与哮喘生命早期感染的风险、加重，和降低肺功能的关系
下一篇：
哮喘患者并发症对生产力损失的影响
