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Association of NRF2 and NQO1 Polymorphisms and Susceptibility to Emphysema
Author(s) -
Marzec Jacqui M,
Hertzberg Andrew,
Yoon HyoungKyu,
Kleeberger Steve
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.795.10
Subject(s) - allele , oxidative stress , single nucleotide polymorphism , genetics , snp , medicine , polymorphism (computer science) , gene , biology , immunology , genotype
Rationale Emphysema is defined as airway enlargement due to loss of alveolar structure and diminished elasticity, and is mainly caused by cigarette smoking and air pollution. NRF2 activates antioxidants such as NQO1 in response to oxidative stress, and deficiency increases susceptibility to cigarette smoke‐induced emphysema in mice. The objective of this study was to determine whether functional polymorphisms in NRF2 and NQO1 associate with emphysema susceptibility. Methods Emphysema cases and controls were recruited for study. Regions of the NRF2 promoter and NQO1 promoter were amplified from genomic DNA and sequenced. Results Individuals homozygous for the NRF2 rs35652124 G allele were at increased risk for development of emphysema compared to those with wildtype alleles [OR 2.514; CI: 1.173, 5.389]. Individuals homozygous for the NQO1 rs689455 C allele were at decreased risk for emphysema compared to those with wildtype alleles [OR 0.299; CI: 0.124, 0.722]. Conclusions In this translational investigation, we found that the NRF2 rs35652124 and the NQO1 rs689455 mutations confer differential risk of emphysema. Previous investigations demonstrated similar risk effects of NRF2 and NQO1 promoter SNPs for susceptibility to acute lung injury. These investigations suggest that NRF2 and NQO1 are pivotal determinants of susceptibility to oxidative stress‐induced lung diseases.