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 cod ing for N-acetyltransferase agrees with acetylation phenotype in children a t various ages. In 82 Caucasian children aged from I mo to 17 y (57 boys an d 25 girls) and including 37 infants, the acetylation phenotype was evaluat ed from the urinary metabolic ratio of 5-acetylamino-6-formylamino-3-methyl uracil (AFMU) to 1 -methylxanthine (IX) after oral administration of caffei ne. At the same time, by use of PCR and restriction analysis of amplified f ragments 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 th e 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 dete cted. Determination of the relation between the acetylation phenotype and g enotype revealed that 18 children (23%) containing at least one wild-type a llele had AFMU/1X < 0.4 (slow acetylation activity) and 7 (8%) of genotypic ally slow acetylators presented high metabolic ratio thigh acetylation acti vity). 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 s tudies enable the detection of genetic acetylation defect.