Affiliations: Department of Internal Medicine, Chang Gung Memorial
Hospital & Chang Gung University, Keelung, Taiwan | Department of Pathology, Chang Gung Memorial Hospital
& Chang Gung University, Keelung, Taiwan
Abstract: Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protects against
oxidative stress which is important in the pathogenesis of chronic obstructive
pulmonary disease (COPD). Three single nucleotide polymorphisms and 1 triplet
repeat polymorphism are found in the promoter region of the Nrf2 gene.
Molecular haplotyping of the Nrf2 promoter region was performed using DNA
obtained from the peripheral blood of 69 COPD patients. The luciferase
activities of Nrf2 promoter constructs containing all possible
combinations of the 4 polymorphisms were determined and found to differ among
the 16 haplotypes.The haplotypes isolated from the subjects were divided into 3
groups (L: low; M: medium; H: high) on the basis of luciferase activities. The
proportions of subjects belonging to global initiative for chronic obstructive
lung disease stage 3 or 4 decreased from the group with the LL haplotype to
that with the HH haplotype. Presence of the LH or MM haplotype (hazard ratio,
3.36; 95% confidence interval, 1.16–9.69), gender (0.13; 0.02–0.67), and
post-bronchodilator FEV_{1} value of predicted (0.95;
0.91–0.99) are significant predictors of respiratory failure development.The
haplotype of the Nrf2 gene promoter affects its activity, and is
associated with the severity and the development of respiratory failure in COPD.
