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

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSION

Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on expression to COPD onset, for the first time.