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已发表论文
ADRB2 基因的功能性 SNP 上游与 COPD 相关
Authors Li JX, Fu WP, Zhang J, Zhang XH, Sun C, Dai LM, Zhong L, Yu L, Zhang YP
Received 8 September 2017
Accepted for publication 3 November 2017
Published 16 March 2018 Volume 2018:13 Pages 917—925
DOI https://doi.org/10.2147/COPD.S151153
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Professor Hsiao-Chi Chuang
Peer reviewer comments 2
Editor who approved publication: Dr Chunxue Bai
Background: Previous studies have
suggested that β2-adrenergic receptor (ADRB2 ) is associated with COPD.
However, the role of genetic polymorphisms in ADRB2 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 ADRB2 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 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).
Conclusion: Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.
Keywords: β2-adrenergic receptor, ADRB2 , FEV1, lung, polymorphism
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.
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).
Conclusion: Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.
Keywords: β2-adrenergic receptor, ADRB2 , FEV1, lung, polymorphism
