Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans

Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Pharmacogenetics and Genomics (Impact Factor: 3.48). 06/2012; 22(8):620-8. DOI: 10.1097/FPC.0b013e32835516e5
Source: PubMed


Oxidative stress is integral to the development of endothelial dysfunction and cardiovascular disease. As NRF2 is a key transcription factor in antioxidant defense, we aimed to determine whether polymorphisms within the promoter region of the gene encoding NRF2 (NFE2L2) would significantly modify vasodilator responses in humans.
Associations between the -653A/G (rs35652124), -651G/A (rs6706649), and -617C/A (rs6721961) polymorphisms within the NFE2L2 promoter and vascular function were evaluated in healthy African-American (n=64) and white (n=184) individuals. Forearm blood flow (FBF) was measured by strain-gauge venous occlusion plethysmography at baseline and in response to incremental doses of bradykinin or sodium nitroprusside. Forearm vascular resistance (FVR) was calculated as the mean arterial pressure/FBF.
In African Americans, -653G variant allele carriers had significantly lower FBF and higher FVR under basal conditions as well as in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P<0.05 for each comparison). In whites, although no significant associations were observed with the -653A/G genotype, -617A variant allele carriers had significantly higher FVR at baseline and in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P<0.05 for each comparison). The -651G/A polymorphism was not associated with vasodilator responses in either racial group.
Polymorphisms within the NFE2L2 promoter were associated with impaired forearm vasodilator responses in an endothelial-independent manner, suggesting an important role of NRF2 in the regulation of vascular function in humans.

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    • "A recent study demonstrated association between Nrf2 polymorphism and hemodynamic parameters. Polymorphisms (rs35652124 and rs6721961) within the Nrf2 promoter were associated with impaired forearm vasodilator responses in an endothelial-independent manner, suggesting an important role of Nrf2 in the regulation of vascular function in humans 16. These vascular responses have been shown to correlate with vasodilator responses in coronary arteries, and predict the risk of developing cardiovascular disease 22. "
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