Comparison of acetylation phenotype with genotype coding for N-acetyltransferase (NAT2) in children

The present study focused on evaluation of the extent to which genotype coding for N-acetyltransferase agrees with acetylation phenotype in children at various ages. In 82 Caucasian children aged from 1 mo to 17 y (57 boys and 25 girls) and including 37 infants, the acetylation phenotype was evaluated from the urinary metabolic ratio of 5-acetylamino-6-formylamino-3-methyluracil (AFMU) to 1-methylxanthine (1X) after oral administration of caffeine. At the same time, by use of PCR and restriction analysis of amplified fragments of the N-acetyltransferase gene, four nucleotide transitions were identified: 481C-->T (KpnI), 590 G-->A (TaqI), 803 A-->G (DdeI), and 857 G-->A (BamHI). The wild-type allele was detected in 27 (33%) children, and the slow acetylation genotype was found in 55 (67%) children. The results of the study show that the metabolic ratio AFMU/1X could be calculated only in 72 children, because in 10 (14%) infants <20 wk of age, AFMU was not detected. Determination of the relation between the acetylation phenotype and genotype revealed that 18 children (23%) containing at least one wild-type allele had AFMU/1X <0.4 (slow acetylation activity) and 7 (8%) of genotypically slow acetylators presented high metabolic ratio (high acetylation activity). We concluded that the disagreement between the acetylation phenotype and genotype is more often found in the group of children characterized by low AFMU/1X and that in small children only N-acetyltransferase genotype studies enable the detection of genetic acetylation defect.