PharmGKB summary

Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in cryopreserved human hepatocytes

“…Genetic polymorphism in arylamine N-acetyltransferase 2 (NAT2) modifies the therapeutic efficacy and toxicity of numerous drugs (Weber and Hein, 1985; McDonagh et al, 2014). Human NAT2 also catalyzes the N-acetylation and O-acetylation of xenobiotics and carcinogens (Hein 1988).…”

N-Acetyltransferase 2: ultra-slow acetylators enter the stage

“…Patterns of polymorphisms-so-called haplotypes or NAT2 allelesresult in a reduced N-, O-and N,O-acetylation of aromatic and heterocyclic amines-in general rather due to a reduction in protein as due to structural changes in the enzyme (McDonagh et al 2014;Hein et al 2008). Persons with an impaired NAT2 capacity-so-called slow acetylatorshave two slow copies of the gene, whereas the presence of one or two rapid or wild-type copies of the gene leads to an intermediate or rapid genotype-so-called rapid acetylators.…”

Differentiation of N-acetyltransferase 2 (NAT2) rapid and intermediate acetylator based on genotype and urinary assay

“…The distributions of NAT2 allele variant in our result are similar to that previously reported study in Javanese-Sundanese ethnic of Indonesia population 14 Examination on NAT2 activity were using urinary caffeine metabolite analysis that widely used as a non-toxic drug in vivo for predicting acetylator phenotype. 8 Our urinary analysis result demonstrates the deduced acetylation status from (AFMU+AAMU)/(AFMU+AAMU+1U+1X) ratios assigned to each NAT2 allele combination detected in this study. The ratio of urinary caffeine metabolites in healthy samples showed that metabolic ratio of rapid acetylator group (0,5) was higher than the one of intermediate group (0,28) (Figure 1).…”

“…8,11 Additionally, the phenotype analysis, usually accommodated only bimodal distribution (slow and rapid group) 12,13 and does not differentiate between the intermediate group from the rapid group. Therefore, in the present study we conducted a study to define the rapid and intermediate NAT2 phenotype based on both genotyping and urinary assay and determine the concordance rate between both methods.…”

“…Individuals can be classified as slow or rapid acetylators, on the basis of their NAT2 genotype, 6,7 although some authors consider a third intermediate category. 1,8,9 Slow (SA), intermediate (IA) and rapid acetylators (RA) consisted of homozygous of two slow alleles, heterozygous between rapid and slow allele and homozygous of two rapid alleles, respectively.…”