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 fra gment length polymorphism method. The rapid-type NAT24 was expressed at a higher frequency (68.6%) than the slow-type genes with specific p oint mutations (NAT26A, 19.3%; NAT2*7B, 9.7%; NAT2*5B, 2.4%). The fre quency of NAT2 genotypes consisted of 44% of a homozygote of NAT2*4, 49% of a heterozygote of NAT24 and mutant genes, and 7% of a combinat ion of mutant genes. The metabolic activity for procainamide to N-acet ylprocainamide was measured in 11 healthy subjects whose genotype had been determined. Although the acetylation activity substantially varie d interindividually, the variability was considerably reduced after cl assification according to the genotype. The N-acetylprocainamide/proca inamide ratio in urinary excretion was 0.60 +/- 0.17 (mean +/- SD) for those with NAT24/*4, 0.37 +/- 0.06 for NAT2*4/*6A, 0.40 +/- 0.03 for NAT24/*7B, and 0.17 for NAT2*6A/*7B. The results indicated that the NAT2 genotype correlates with acetylation of procainamide.