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标题：Heme oxygenase 1 polymorphism, occupational vapor, gas, dust, and fume exposure and chronic obstructive pulmonary disease in a Danish population-based study
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作者：Würtz ET ; Brasch-Andersen C ; Steffensen R 等
期刊名称：Scandinavian journal of Work, Environment and Health
印刷版ISSN：0355-3140
出版年度：2020
卷号：46
期号：1
页码：96-104
DOI：10.5271/sjweh.3846
语种：English
出版社：National Board of Occupational Safety and Health
摘要：Objectives The number of dinucleotide repeats (GT) n modulate expression of heme oxygenase 1 ( HMOX1 ), a stress response gene. Multiple repeats might affect chronic obstructive pulmonary disease (COPD) susceptibility. We aimed to investigate the association of this polymorphism with COPD and its interaction with occupational exposures (vapor, gas, dust, or fumes).Methods This population-based cross-sectional study included 4703 Danes, aged 45–84 years. HMOX1 (GT) n was genotyped and grouped as short: 26, medium: 27–32 and long: =33 alleles. COPD was defined by the lower limit of normal (2.5 th FEV 1 /FVC and FEV 1 centiles). Occupational exposure was defined as ever exposed to vapor, gas, dust, or fume in expert-selected jobs. Associations were analyzed by adjusted mixed logistic regression.Results The population included 6% with COPD, 48% who had smoked =10 pack-years, and 46% with occupational exposure. HMOX1 was genotyped in 4423 participants. The adjusted odds ratio (OR) for the association between HMOX1 long allele and COPD was 1.75 [95% confidence interval (CI) 1.18–2.60]. An interaction was evident between HMOX1 long allele and occupational exposure, OR 2.38 (95% CI 1.04–5.46), versus HMOX1 short/medium without exposure. Analyses were replicated in another cohort, aged 20–44 years, N=1168, including 3% with COPD, 25% who had smoked =10 pack-years and 20% with occupational exposure. No associations were seen between COPD and HMOX1 long allele here.Conclusions Long alleles in HMOX1 alone and in interaction with occupational exposure seem to be associated with COPD. Failure to replicate data may be due to premature age for COPD development and low occupational exposure prevalence. We propose this long allele may be a genetic contributor to the COPD pathogenesis.
关键词：chronic obstructive pulmonary disease; COPD; Denmark; dust; dust exposure; exposure; fume; fume exposure; gas; gas exposure; gene-by-occupational interaction; genetic effect; heme oxygenase 1 polymorphism; HMOX1; lung function; occupational exposure; occupational exposure; population-based study; rs3074372; vapor; vapor exposure