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 NAT2*4 was expressed at a higher frequency (68.6%) than the slow-type genes with specific point mutations (NAT2*6A, 19.3%; NAT2*7B, 9.7%; NAT2*5B, 2.4%). The frequency of NAT2* genotypes consisted of 44% of a homozygote of NAT2*4, 49% of a heterozygote of NAT2*4 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 NAT2*4/*6A, 0.40 +/- 0.03 for NAT2*4/*7B, and 0.17 for NAT2*6A/*7B. The results indicated that the NAT2* genotype correlates with acetylation of procainamide.
Okumura
K
K
Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan. okumurak@icluna.kobe-u.ac.jp
Kita
T
T
Chikazawa
S
S
Komada
F
F
Iwakawa
S
S
Tanigawara
Y
Y
D000120:Acecainide / Q000097:blood / Q000652:urine; D000107:Acetylation; D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000097:blood / Q000235:genetics* / Q000652:urine; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011342:Procainamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D010975:Platelet Aggregation Inhibitors; D004247:DNA; D000120:Acecainide; D001191:Arylamine N-Acetyltransferase; D011342:Procainamide