Pitfalls in N-acetyltransferase 2 genotyping

In recent times, an increasing number of different haplotypes of the arylamine N-acetyltransferase 2 gene are reported. Since most of the various alleles are defined by linkages of commonly known hereditary point mutations, some confusion may occur when the mutation pattern revealed by genotyping should be addressed correctly to defined haplotypes. Moreover, problems take place when different nomenclatures are incorrectly transferred. To meet growing concerns regarding exact NAT2 genotyping and correct nomenclature, we summarized typical pitfalls in methodologies and terminologies. NAT2 genotypes containing rare alleles, or even combinations of them, should always be checked critically for possible laboratory failures. Novel alleles should be best verified by subcloning or other adequate methodologies. For prediction of the acetylator phenotype it seems generally sufficient to genotype NAT2 mutations C282T and T341C. In African populations, however, it is necessary to check additionally for the frequent G191A mutation, which codes also for a slow acetylator variant.