Nrf2 Pathway

DetoxThis is part of an ongoing series on the genes involved in detoxification.

The Nrf2 signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes.  In my mind, it flips the switch to call up the phase II enzymes to take out the trash produced in phase I detox.  The phase II enzymes then further breakdown the metabolites from phase I and make them into something that can be excreted by the body.  Specifically, the Nrf2 signaling pathway is involved in GSTs, NQO1, UGTs, and SULTs.

Sulforaphane (broccoli, Brussels sprouts, cabbage, cauliflower) is thought to activate the Nrf2 pathway.  Green tea, garlic, turmeric, and DHA also activate Nrf2.  There are also several companies (some multi-level-marketing) promoting supplements that activate Nrf2, so a lot of Google searches turn up promotional information for these supplements.

Polymorphisms

Polymorphisms in the NFE2L2 (Nrf2 pathway) gene are fairly common, with some polymorphisms seeming to increase Nrf2 pathway signaling and some diminishing it.  Some of these are being studied in relation to cancer prognosis, lung volume in smokers, and Parkinson’s disease.  Most of what I found was fairly recent, so this would be something to keep reading about over the next few years.

Check your 23andMe results for rs6726395:

  • GG:  greater lung volume in smokers [ref], decreased risk of AMD [ref]
  • AG: somewhat greater lung volume in smokers
  • AA: normal

 

Check your 23andMe results for rs1806649:

  • CC:  common
  • TT: significantly reduced risk of death from COPD [ref]

 

Check your 23andMe results for rs6721961:

  • GG:  common
  • TT: significantly diminished Nrf2 expression, increased risk of lung cancer [ref]

 

More to read:

Video explaining Nrf2: https://www.youtube.com/watch?v=-pH9SOB_R1Q

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