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Disease Markers
Volume 28, Issue 3, Pages 185-193
http://dx.doi.org/10.3233/DMA-2010-0700

Functional Haplotypes in the Promoter Region of Transcription Factor Nrf2 in Chronic Obstructive Pulmonary Disease

Chung-Ching Hua,1 Liang-Che Chang,2 Jo-Chi Tseng,1 Chien-Ming Chu,1 Yu-Chih Liu,1 and Wen-Bin Shieh1

1Department of Internal Medicine, Chang Gung Memorial Hospital & Chang Gung University, Keelung, Taiwan
2Department of Pathology, Chang Gung Memorial Hospital & Chang Gung University, Keelung, Taiwan

Received 1 June 2010; Accepted 1 June 2010

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 FEV1 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.