TY - JOUR
T1 - Heme oxygenase 1 polymorphism, occupational vapor, gas, dust, and fume exposure and chronic obstructive pulmonary disease in a Danish population-based study
AU - Würtz, Else Toft
AU - Brasch-Andersen, Charlotte
AU - Steffensen, Rudi
AU - Hansen, Jens Georg
AU - Malling, Tine Halsen
AU - Schlünssen, Vivi
AU - Omland, Øyvind
PY - 2020
Y1 - 2020
N2 - Objectives The number of dinucleotide repeats (GT) nmodulate 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) nwas genotyped and grouped as short: ≤26, medium: 27-32 and long: ≥33 alleles. COPD was defined by the lower limit of normal (2.5 thFEV 1/FVC and FEV 1centiles). 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.
AB - Objectives The number of dinucleotide repeats (GT) nmodulate 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) nwas genotyped and grouped as short: ≤26, medium: 27-32 and long: ≥33 alleles. COPD was defined by the lower limit of normal (2.5 thFEV 1/FVC and FEV 1centiles). 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.
KW - COPD
KW - Denmark
KW - Dust exposure
KW - Gas exposure
KW - Gene-by-occupational interaction
KW - Genetic effect
KW - HMOX1
KW - Lung function
KW - Occupational exposure
KW - Rs3074372
KW - Vapor exposure
UR - http://www.scopus.com/inward/record.url?scp=85077403472&partnerID=8YFLogxK
U2 - 10.5271/sjweh.3846
DO - 10.5271/sjweh.3846
M3 - Journal article
C2 - 31411335
SN - 0355-3140
VL - 46
SP - 96
EP - 104
JO - Scandinavian Journal of Work, Environment & Health
JF - Scandinavian Journal of Work, Environment & Health
IS - 1
ER -