International journal of chronic obstructive pulmonary disease · 2018
A functional SNP upstream of the ADRB2 gene is associated with COPD.
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Li Jin-Xiu, Fu Wei-Ping, Zhang Jing, Zhang Xiao-Hua, Sun Chang, Dai Lu-Ming, Zhong Li, Yu Li, Zhang Ya-Ping
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAgedBinding SitesCase-Control StudiesCell LineChi-Square DistributionChinaFemaleForced Expiratory VolumeGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHumansLogistic ModelsLungMaleMiddle AgedNeurofibromin 1Odds RatioPhenotypePolymorphism, Single NucleotidePromoter Regions, GeneticPulmonary Disease, Chronic ObstructiveReceptors, Adrenergic, beta-2Risk FactorsVital Capacity