Functional haplotypes in the promoter region of transcription factor Nrf2 in chronic obstructive pulmonary disease.
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.
Department of Internal Medicine, Chang Gung Memorial Hospital & Chang Gung University, Keelung, Taiwan.
Chung-Ching
CC
Hua
Liang-Che
LC
Chang
Jo-Chi
JC
Tseng
Chien-Ming
CM
Chu
Yu-Chih
YC
Liu
Wen-Bin
WB
Shieh
D001483:Base Sequence; D017931:DNA Primers; D006239:Haplotypes; D006801:Humans; D016297:Mutagenesis, Site-Directed; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*
D017931:DNA Primers; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human