Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

You are here: Pharmacogenetics » N-Acetyltransferase-related drug intolerance

N-Acetyltransferase-related drug intolerance [T88.7]

OMIM numbers: 243400, 612182 (NAT2)

Dipl.-Biol. Birgit Busse

Scientific Background

Detoxification of drugs and xenobiotics by acetylation in the human organism is catalyzed by the N-acetyltransferases NAT1 and NAT2. Differences in the metabolism of the tuberculostatic isoniazid, caused by the acetylation status of the patient, have been observed already 50 years ago. There are three existing phenotypes of acetylators – the rapid (RA), the slow (SA) and the intermediate (IA) acetylator. The slow acetylator (SA) phenotype is caused by homozygous or combined heterozygous variants in the coding region of the NAT2 gene, with four prevalent variant alleles (NAT2*5a/b, *6a, *7a/b, *14a). Adverse drug reactions due to NAT2 manifest in slow acetylators as peripheral neuropathy under treatment with isoniazid or as hypersensitivity towards sulphonamides and in rapid acetylators in leukopenia under treatment with amonafide, a chemotherapeutic prodrug. Prevalence of the variant NAT2 alleles varies strongly according to ethnicity: while 40-70% of the population in Europe are slow acetylators, 90% of the Northern African population and only 10% of the oriental population are slow acetylators.