NAT2

NAT2 is the gene encoding the enzyme N-acetyltransferase 2, a cytosolic enzyme of the N-acetyltransferase family that catalyzes the N-acetylation of arylamines and hydrazines, facilitating the metabolism and elimination of both drugs and carcinogens.

The NAT2 gene is located on chromosome 8p22 and is expressed mainly in the liver and intestines, with activity in other tissues.

NAT2 is highly polymorphic; genetic variation leads to distinct acetylation phenotypes: fast and slow. The most common fast allele is NAT2*4; many alleles such as NAT2*5, NAT2*6, and NAT2*7 are associated with reduced enzyme activity, often resulting in a slow acetylator phenotype when present in diplotype combination. The acetylation rate influences plasma levels and effects of substrates.

In pharmacology, NAT2 status affects the metabolism of drugs including isoniazid, procainamide, hydralazine, and certain sulfonamides. Slow acetylators may experience higher systemic exposure and toxicity with these drugs, while fast acetylators may clear them more rapidly, potentially reducing efficacy for some agents. Genotyping or phenotyping for NAT2 is used in research and, in some cases, to guide dosing, though routine clinical testing is not universal.

In cancer epidemiology, NAT2-mediated metabolism can modulate the activation or detoxification of aromatic amine carcinogens; slow acetylator status has been associated with increased risk of bladder cancer in individuals exposed to such carcinogens in some studies, but results vary by population and exposure.