Li Jin-Xiu, Fu Wei-Ping, Zhang Jing, Zhang Xiao-Hua, Sun Chang, Dai Lu-Ming, Zhong Li, Yu Li, Zhang Ya-Ping
State Key Laboratory for Conservation and Utilization of Bio-Resource in Yunnan.
Key Laboratory for Animal Genetic Diversity and Evolution of High Education in Yunnan Province, School of Life Sciences, Yunnan University.
Int J Chron Obstruct Pulmon Dis. 2018 Mar 16;13:917-925. doi: 10.2147/COPD.S151153. eCollection 2018.
Previous studies have suggested that β-adrenergic receptor () is associated with COPD. However, the role of genetic polymorphisms in on COPD has not been evaluated yet.
In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between genetic polymorphisms and COPD, comprehensively.
One single nucleotide polymorphism (rs12654778), located upstream of , showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (=0.04) in 200 COPD patients and 222 controls from southwest Chinese population. Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (=0.0034). The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1. In addition, a significantly reduced expression of in COPD patients was observed, compared with normal controls (=0.017).
Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on expression to COPD onset, for the first time.
先前的研究表明β-肾上腺素能受体（）与慢性阻塞性肺疾病（COPD）有关。然而，基因多态性在COPD中的作用尚未得到评估。
在本研究中，采用SNaPshot基因分型、荧光素酶测定、染色质免疫沉淀和实时聚合酶链反应全面研究基因多态性与COPD之间的关联。
位于上游的一个单核苷酸多态性（rs12654778），在对来自中国西南人群的200例COPD患者和222例对照进行年龄、性别和吸烟史校正后，经逻辑回归分析显示与COPD存在显著关联（=0.04）。此外，荧光素酶测定表明，与rs12654778-G等位基因相比，rs12654778-A等位基因使相对启动子活性降低了约26%（=0.0034）。染色质免疫沉淀分析表明rs12654778调节了转录因子神经纤维瘤蛋白1的结合亲和力。此外，与正常对照相比，COPD患者中观察到显著降低的表达（=0.017）。
我们的研究结果首次表明了一种先前未知的机制，将rs12654778对表达的等位基因特异性效应与COPD发病联系起来。
