Genotyping of N-acetylation polymorphism and correlation with procainamide metabolism.

We studied the genotypes of polymorphic N-acetyltransferase (NAT2) in 145 Japanese subjects by the polymerase chain reaction-restriction fragment length polymorphism method. The rapid-type NAT24 was expressed at a higher frequency (68.6%) than the slow-type genes with specific point mutations (NAT26A, 19.3%; NAT27B, 9.7%; NAT25B, 2.4%). The frequency of NAT2* genotypes consisted of 44% of a homozygote of NAT24, 49% of a heterozygote of NAT24 and mutant genes, and 7% of a combination of mutant genes. The metabolic activity for procainamide to N-acetylprocainamide was measured in 11 healthy subjects whose genotype had been determined. Although the acetylation activity substantially varied interindividually, the variability was considerably reduced after classification according to the genotype. The N-acetylprocainamide/procainamide ratio in urinary excretion was 0.60 +/- 0.17 (mean +/- SD) for those with NAT2*4/4, 0.37 +/- 0.06 for NAT24/6A, 0.40 +/- 0.03 for NAT24/7B, and 0.17 for NAT26A/7B. The results indicated that the NAT2 genotype correlates with acetylation of procainamide.