Occupational COPD and HMOX1 repeats in a Danish population

Background: Dinucleotide repeats (GT)n in the 5’prime promoter region of the heme oxygenase 1 (HMOX1) gene modulate the gene expression. Long repeats might affect occurrence of COPD. We aimed to investigate associations of the HMOX1 polymorphism of (GT)n repeats to occurrence of COPD.Methods: This population based cohort included 4703 Danes aged 45-84 of Northern European descents. COPD was defined by LLN: 2.5th FEV1/FVC and FEV1 centiles. The occupational exposures were defined as years with vapour, gas, dust or fume (VGDF) exposure. The HMOX1 repeat was genotyped by fragment analysis and capillary electrophoresis and grouped according to short (S): ≤26, medium (M): 27-32 and long (L): ≥33 GT repeat alleles in an L dominant genetic model. Associations were analysed with mixed random effect logistic regression adjusted for smoking, sex, occupational exposure, age and general practitioner practice. Currently, analyses are attempted replicated in a younger Danish cohort aged 20-44.Results: A HMOX1 (GT)n genotype was present in 4423 participants and distributed as S/S 12%, S/M 42%, M/M 35%, S/L 4%, M/L 7% and L/L 0.1%. The crude association between COPD and at least one long GT repeat (S/L, M/L, L/L) GT genotype was significant, p<0.01. After adjustment, parts of all variables were significantly associated to COPD. The odds ratio for the HMOX1 L dominant variable and COPD was 1.74 (95% CI: 1.17-2.59) and for 5-14 years VGDF exposure and COPD OR 1.62 (95% CI: 1.02-2.56).Conclusion: The study supports an association between occupational exposure and COPD with HMOX1 repeats in the model. The association of a long GT repeat in HMOX1 seems to be comparable to a medium occupational VGDF exposure.