N-acetyltransferase is a phase II detoxification enzyme that helps to metabolize aromatic amines, drugs, cigarette smoke, and carcinogens. Basically, it makes specific toxins more water soluble so that they can be excreted through a process called acetylation.

There are several common genetic variants that can classify a person as a slow, intermediate, or rapid acetylator. Although the rapid acetylator is considered to be the ancestral type and is the most common type in Asian and African populations, Caucasian people are actually slightly more likely to be intermediate or slow acetylators.[ref]

Historically, N-acetyltransferase was first recognized in the 1950’s to play a role in the metabolism of tuberculosis drug. A significant percentage of people were found to be poor acetylators resulting in significant side effects of the tuberculosis drug, isoniazid.

Genetic variants involved:

NA/T1 metabolizes p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS).[ref] PABA used to be commonly found in sunscreens, and PAS is used as an antibiotic for tuberculosis. It also breaks down components of cigarette smoke and heterocyclic aromatic amines, which forms when meats and seafood are grilled at high temperatures.

There have been studies linking NA/T1 genetic variants to an increased risk of bladder, colon, breast, lung, prostate, and pancreatic cancers. [ref]

Smoking is even more risky for those with NA/T1 slow acetylator variants. NA/T1 slow and intermediate acetylators had been shown to have a significantly higher risk for esophageal cancer and lung cancer in smokers.[ref]

It has recently been found that NA/T1 slow acetylators have more DNA adducts formed with heterocyclic aromatic amines (carcinogens from meat being cooked at high temps). [ref]  Another study also found red meat consumption for slow and intermediate acetylators to be linked to esophageal cancer. [ref]

NA/T1 is also involved in folate metabolism and folate may be a co-enzyme for NA/T1 hydrolysis of acetyl-Coenzyme A [ref].  Rs15561 -A/A (below) has been associated with cleft lip (especially if the mother smokes) and spina bifida. Note that it is the baby’s genotype, not the mother’s, that is being studied, so this is another really good reason not to smoke. [ref] Both of those conditions are linked to folate metabolism and the methylation cycle.

Check your 23andMe results for rs4986782:

  • A/A: NA/T1*14B, slow acetylator [ref]
  • A/G: slow acetylator,
  • G/G: normal

 

Check your 23andMe results for rs15561:

  • A/A: reduced function [ref]
  • A/C: reduced function
  • C/C: normal

 

Check your 23andMe results for rs6586714:

  • A/A: lower risk of colon cancer from cooked meat carcinogens (protective) [ref]
  • A/G: lower risk of colon cancer from a cooked meat carcinogens
  • G/G: wildtype/common

There are several other SNPs that are not included in 23andMe data so the above SNPs are not the complete picture for NA/T1.

NA/T2 also catalyzes the acetylation of a couple of types of carcinogens (aromatic and heterocyclic amines) which include tobacco smoke, well-cooked meat, and exhaust fumes. NA/T2 is found mainly in the liver, in contrast with NA/T1, which is found throughout the body. NA/T2 has been studied extensively and is thought to play a role in the risk for several types of cancers.

NA/T2 polymorphisms also create rapid, intermediate, and slow acetylators. Slow acetylators don’t clear out toxins as well and are at a somewhat higher risk for bladder, lung, breast, and esophageal cancers. Rapid acetylators can actually make some toxins more reactive and may be at a slightly higher risk for colon cancer.

There is an online tool from the University of Albany to determine your NA/T2 phenotype.  http://nat2pred.rit.albany.edu/  You will need to look up your data for six different SNPs.   It asks you to put in your NA/T2 alleles for the following:

NA/T2 rs1208 – A, has also been found to be involved in increased insulin resistance, although, to me, the effect looked pretty small.  [ref]

NA/T is also being studied in relation to bacteria which can produce it, and their relationship to drug metabolism.


Lifehacks

If you need another reason not to smoke, being a slow or intermediate acetylator is a really good reason to never pick up a cigarette.

Slow acetylators may want to cut back on fried meats to limit the intake of heterocyclic aromatic amines.

Further reading:

Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery


Leave a Reply

Your email address will not be published. Required fields are marked *

Related Posts

Disease Prevention

Back Pain and Your Genes

For some people, back pain is a daily occurrence that drastically affects their quality of life. For others, it may be an intermittent nagging problem that pops up occasionally, often without rhyme or reason. If you Read more…

Disease Prevention

Heart attack risk and hantavirus protection

Say that you slip with the knife while cutting up an apple for lunch. Ouch. It may bleed a bit, but you know that pretty soon it will stop. A whole cascade of events takes place Read more…

Alzheimer's

Melatonin: Key to Health and Longevity

It seems like everything that I’ve written about lately has a common thread: melatonin. When I started weaving together all those melatonin threads, a big picture was revealed. You could say it is a… tapestry Read more…