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:

NAT1 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 NAT1 genetic variants to an increased risk of bladder, colon, breast, lung, prostate, and pancreatic cancers. [ref]

Smoking is even more risky for those with NAT1 slow acetylator variants. NAT1 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 NAT1 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]

NAT1 is also involved in folate metabolism and folate may be a co-enzyme for NAT1 hydrolysis of acetyl-Coenzyme A [ref].  Rs15561 -AA (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:

  • AA: NAT1*14B, slow acetylator [ref]
  • AG: slow acetylator,
  • GG: normal

 

Check your 23andMe results for rs15561:

  • AA: reduced function [ref]
  • AC: reduced function
  • CC: normal

 

Check your 23andMe results for rs6586714:

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

There are several other SNPs that are not included in 23andMe data so the above SNPs are not the complete picture for NAT1.

NAT2 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. NAT2 is found mainly in the liver, in contrast with NAT1, which is found throughout the body. NAT2 has been studied extensively and is thought to play a role in the risk for several types of cancers.

NAT2 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 NAT2 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 NAT2 alleles for the following:

NAT2 rs1208 – A, has also been found to be involved in increased insulin resistance, although, to me, the effect looked pretty small.  [ref]

NAT 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

Detox

BPA: How Your Genes Influence BPA Detoxification

BPA, a chemical found in some plastics, has been linked to a variety of effects on people including obesity, insulin resistance, and epigenetic effects on the fetus.  It is everywhere in our food supply. In Read more…

Circadian Rhythm

Early to bed, early to rise – helps with weight loss and diabetes

This one simple change can help you lose weight and prevents diabetes! Ok, enough with the smarmy copywriting hooks… I’m going to depart from my usual format of talking about a specific genetic variant and Read more…

Diet / Gene Interaction

Should I Take Aspirin to Prevent Heart Disease?

Everyone knows that aspirin protects against heart disease, right? Well, it turns out that aspirin may only protect some people from heart disease, and for others, it can actually slightly increase the risk of heart disease. Read more…