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

Rika Yuliwulandari, Kinasih Prayuni, Herman Usman, Qomariyah Sachrowardi, Katsushi Tokunaga


Determination of the acetylator type of NAT2 generally can be predicted based on genotype data from the NAT2 database. However, in some reported studies, it does not show 100 per cent concordance with the phenotype based on urinary assay. The assay generally only differentiates the rapid and slow acetylator but does not consider the intermediate one.

We conducted this study to define the phenotype of NAT2 based on both genotyping and urinary assay and to determine the concordance rate between both methods in rapid and intermediate acetylator groups.

NAT2 genotyping was done using the PCR-direct sequencing in a total of 30 healthy subjects. However, for the NAT2 phenotypes we only selected 19 healthy subjects that carry rapid or intermediate acetylator genotype, without involving slow acetylator phenotype. The assay was done by measuring the ratios of urinary caffeine metabolites following controlled diet exposure.

Both data obtained from genotyping and urinary assay showed 2 samples that belonged to the rapid acetylator and 17 samples that belonged to the intermediate acetylator. The mean metabolic ratio of the rapid acetylator group showed a higher level (0.5) than the intermediate group (0.28). The predicted acetylation status of NAT2 SNPs from genotyping was matched with the phenotype which was determined by urinary analysis.

Our result showed a 100 per cent concordance of NAT2 phenotype based on the genotyping and urinary assay. Based on this study we suggest that NAT2 phenotype based on genotyping method is simpler and faster, rather than using the urinary assay that is more laborious and costly.
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