The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
Shenzhen Guangming district center for disease control and prevention, Shenzhen 518106, China.
Sci Rep. 2017 Jan 12;7:40060. doi: 10.1038/srep40060.
It is highly possible that copy number variations (CNVs) in susceptible regions have effects on chronic obstructive pulmonary disease (COPD) development, while long noncoding RNA (lncRNAs) have been shown to cause COPD. We hypothesized that the common CNV, named nsv823469 located on 6p22.1, and covering lncRNAs (major histocompatibility complex, class I, A (HLA-A) and HLA complex group 4B (HCG4B)) has an effect on COPD risk. This association was assessed through a two-stage case-control study, and was further confirmed with COPD and pulmonary function-based family analyses, respectively. The copy number loss (0-copy/1-copy) of nsv823469 significantly decreased risk of COPD compared with normal (2-copy) (OR = 0.77, 95% CI = 0.69-0.85). The loss allele, inducing copy number loss of nsv823469, has a tendency to transmit to offspring or siblings (P = 0.010) and is associated with forced expiratory volume in 1 second (FEV1) (P = 0.030). Furthermore, the copy number loss of nsv823469 in normal pulmonary tissue decreases the expression levels of HCG4B (r = 0.315, P = 0.031) and HLA-A (r = 0.296, P = 0.044). Our data demonstrates that nsv823469 plays a role in COPD and pulmonary function inheritance by potentially altering expression of HCG4B.
位于 6p22.1 上的常见拷贝数变异 (CNV) nsv823469 可影响慢性阻塞性肺疾病 (COPD) 的发展，而长非编码 RNA (lncRNA) 已被证明可导致 COPD。我们假设常见的 CNV，命名为 nsv823469，位于 6p22.1 上，覆盖 lncRNA（主要组织相容性复合体，I 类，A（HLA-A）和 HLA 复合物组 4B（HCG4B）），对 COPD 风险有影响。通过两阶段病例对照研究评估了这种关联，并分别通过 COPD 和基于肺功能的家族分析进一步证实了这种关联。与正常（2 拷贝）相比，nsv823469 的拷贝数缺失（0 拷贝/1 拷贝）显著降低了 COPD 的风险（OR=0.77，95%CI=0.69-0.85）。nsv823469 的缺失等位基因，导致 nsv823469 的拷贝数缺失，有倾向将其传递给后代或兄弟姐妹（P=0.010），并且与 1 秒用力呼气量（FEV1）相关（P=0.030）。此外，nsv823469 在正常肺组织中的缺失降低了 HCG4B（r=0.315，P=0.031）和 HLA-A（r=0.296，P=0.044）的表达水平。我们的数据表明，nsv823469 通过潜在改变 HCG4B 的表达，在 COPD 和肺功能遗传中发挥作用。
