NAT2 Genotyping

The enzyme arylamine N-acetyltransferase 2 (NAT2) metabolizes compounds that are foreign to the body (e.g, pesticides, cancer-causing chemicals), as well as therapeutic medications. Mutations in the gene encoding NAT2 may cause a decrease in NAT2 activity, resulting in potential adverse effects. In some cases, a decrease in NAT2 activity may increase medication effectiveness (e.g., hydralazine). Isoniazid, hydralazine, and certain sulfonamides have the most evidence for variations in individuals drug response caused by NAT2 polymorphisms. These drugs are frequently used as part of the treatment for infection, tuberculosis, and cardiovascular disease.[58] Additionally, mutations in the NAT2 gene are tentatively associated with certain cancers and other disease states, but in most cases, more evidence is needed. Genetic alleles tested for NAT2 are *4,*5A-E,*5G,*5J,*6A-C,*6E,*7A,*7B,*11,*12A-D,*13,*14A-G,*19.

Indications for NAT2 Testing

Individuals who have a personal or family history of adverse effects with medications metabolized by NAT2 or who are currently undergoing or will undergo isoniazid, hydralazine, or sulfonamide (e.g., sulfamethoxazole, sulfasalazine (Azulfidine®), etc.) therapy should be considered for NAT2 testing. In general, assessment of medical necessity for testing is up to the provider’s clinical judgment.