Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury.

Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Research Abstract Details 

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Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Abstract Text:

Jacqui M Marzec,Jason D Christie,Sekhar P Reddy,Anne E Jedlicka,Hue Vuong,Paul N Lanken,Richard Aplenc,Tae Yamamoto,Masayuki Yamamoto,Hye-Youn Cho,Steven R Kleeberger,

We recently used positional cloning to identify the transcription factor Nrf2 (NF-E2 related factor 2) as a susceptibility gene in a murine model of oxidant-induced acute lung injury (ALI). NRF2 binds to antioxidant response elements (ARE) and up-regulates protective detoxifying enzymes in response to oxidative stress. This led us to investigate NRF2 as a candidate susceptibility gene for risk of development of ALI in humans. We identified multiple single nucleotide polymorphisms (SNPs) by resequencing NRF2 in ethnically diverse subjects, and one (-617 C/A) significantly (P<0.001) diminished luciferase activity of promoter constructs containing the SNP and significantly decreased the binding affinity (P<0.001) relative to the wild type at this locus (-617 CC). In a nested case-control study, patients with the -617 A SNP had a significantly higher risk for developing ALI after major trauma (OR 6.44; 95% CI 1.34, 30.8; P=0.021) relative to patients with the wild type (-617 CC). This translational investigation provides novel insight into the molecular mechanisms of susceptibility to ALI and may help to identify patients who are predisposed to develop ALI under at risk conditions, such as trauma and sepsis. Furthermore, these findings may have important implications in other oxidative stress related illnesses.

Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Publishing Authors By Initials

JM Marzec,JD Christie,SP Reddy,AE Jedlicka,H Vuong,PN Lanken,R Aplenc,T Yamamoto,M Yamamoto,HY Cho,SR Kleeberger,

For similar biological phenomena, cell phenomena, and immunity: immunity: antibody specificity: species specificity research abstracts see: biological phenomena, cell phenomena, and immunity: immunity: antibody specificity: species specificity research

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Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The FASEB journal : official publication of the Fe

VOLUME: 21

Page Numbers: 2237-46

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 23

MONTH: 03

YEAR: 2007

Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Information

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LANGUAGE: eng

NlmUniqueID: 8804484

Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Keywords Mesh Terms:

KEYWORDS: Species Specificity

MESH TERMS: genetics

Chemical & Substance for Abstract: Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Information

Substance Name: NFE2L2 protein, human

Registry Number: 0

Grant and Affiliation Information for Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury.

AFFILIATION: Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL-66109

ACRONYM: HL

MEDLINETA: FASEB J

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