Background: Previous studies have suggested that β 2 -adrenergic receptor (ADRB2) is associatedwith COPD. However, the role of genetic polymorphisms in ADRB2 on COPD has not beenevaluated yet.

Methods: In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitationand real-time polymerase chain reaction were adopted to investigate the association betweenADRB2 genetic polymorphisms and COPD, comprehensively.

Results: One single nucleotide polymorphism (rs12654778), located upstream of ADRB2,showed a significant association with COPD by the logistic regression analysis after adjusting forage, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwestChinese population. Furthermore, the luciferase assay indicated that rs12654778-A allele reducedthe relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034). Thechromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the bindingaffinity of transcription factor neurofibromin 1. In addition, a significantly reduced expressionof ADRB2 in COPD patients was observed, compared with normal controls (p=0.017).

Conclusion: Our findings suggest a previously unknown mechanism linking allele-specificeffects of rs12654778 on ADRB2 expression to COPD onset, for the first time.