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A functional SNP upstream of the ADRB2 gene is associated with COPD.

Authors :: Li JX
Fu WP
Zhang J
Zhang XH
Sun C
Dai LM
Zhong L
Yu L
Zhang YP
Source :: International journal of chronic obstructive pulmonary disease [Int J Chron Obstruct Pulmon Dis] 2018 Mar 16; Vol. 13, pp. 917-925. Date of Electronic Publication: 2018 Mar 16 (Print Publication: 2018).
Publication Year :: 2018
Abstract: Background: Previous studies have suggested that β <subscript>2</subscript> -adrenergic receptor ( ADRB2 ) is associated with COPD. However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet.<br />Methods: In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively.<br />Results: One single nucleotide polymorphism (rs12654778), located upstream of ADRB2 , showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history ( p =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 ( p =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 ADRB2 in COPD patients was observed, compared with normal controls ( p =0.017).<br />Conclusion: Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.<br />Competing Interests: Disclosure The authors report no conflicts of interest in this work.