Genetic Impact Ofcdhr3on The Adult Onset Of Asthma And Copd

CLINICAL AND EXPERIMENTAL ALLERGY(2020)

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摘要
Background Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases caused by complex gene-environment interactions. A functional single nucleotide polymorphism of cadherin-related family member 3 (CDHR3), known as a receptor of rhinovirus-C, is associated with childhood-onset asthma especially in atopic individuals. Objective Here, we identified risk factors for adult-onset asthma and COPD, focusing on the impact of theCDHR3variant in atopic individuals. Methods We conducted a longitudinal, retrospective, observational cohort study of 1523 healthy adults with baseline examinations at Tsukuba Medical Center Hospital in 2008 and retrospectively identified new-onset, physician-diagnosed asthma or COPD from 2009 to 2018. We assessed risk factors by the Cox regression analysis. The impact ofCDHR3variant rs6967330 was also examined in individuals with pre-existing atopy. Results Over 10 study years, 103 people developed airway diseases (79 asthma and 24 COPD; 52 females, average onset-age 55 years old, range 38-80). Higher body mass index (BMI) and lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio were significant risk factors (BMI: HR 1.072 [95% CI 1.005-1.14],P = .034; FEV1/FVC ratio: HR 1.091 [1.044-1.14],P = .00011). Restriction to atopic individuals saw the A allele at rs6967330 and lower FEV1/FVC ratio to associate with adult-onset disease (A allele: HR 2.89 [1.57-5.20],P = .00062; FEV1/FVC ratio: HR 1.10 [1.04-1.17],P = .0010). Conclusion and clinical relevance Genetic susceptibility to rhinovirus-C infection in atopic individuals is a risk factor for chronic airway diseases even in later life.
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关键词
adult-onset asthma, atopy, cadherin-related family member 3 (CDHR3), chronic obstructive pulmonary disease (COPD), genetics, rhinovirus
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