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Article type: Research Article
Authors: Hua, Chung-Ching | Chang, Liang-Che | Tseng, Jo-Chi | Chu, Chien-Ming | Liu, Yu-Chih | Shieh, Wen-Bin
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
Note: [] Corresponding author: Liang-Che Chang, Department of Pathology, Chang Gung Memorial Hospital & Chang Gung University, 222 Maijin Road, Keelung 204, Taiwan. Tel.: +886 2 24313131, ext 2641; Fax: +886 2 24313131, ext 2640; E-mail: lc2008@adm.cgmh.org.tw; changlc2008@gmail.com
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.
Keywords: Respiratory failure, COPD, haplotype, Nrf2, promoter
DOI: 10.3233/DMA-2010-0700
Journal: Disease Markers, vol. 28, no. 3, pp. 185-193, 2010
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