Genotyping of N-acetylation polymorphism and correlation with procainamide metabolism

Katsuhiko Okumura, Tomoko Kita, Shinji Chikazawa, Fusao Komada, Seigo Iwakawa, Yusuke Tanigawara

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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 α 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.

Original languageEnglish
Pages (from-to)509-517
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume61
Issue number5
DOIs
Publication statusPublished - 1997 May
Externally publishedYes

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Procainamide
Acetylation
Genotype
Acecainide
Genes
Acetyltransferases
Homozygote
Heterozygote
Point Mutation
Restriction Fragment Length Polymorphisms
Healthy Volunteers
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology

Cite this

Genotyping of N-acetylation polymorphism and correlation with procainamide metabolism. / Okumura, Katsuhiko; Kita, Tomoko; Chikazawa, Shinji; Komada, Fusao; Iwakawa, Seigo; Tanigawara, Yusuke.

In: Clinical Pharmacology and Therapeutics, Vol. 61, No. 5, 05.1997, p. 509-517.

Research output: Contribution to journalArticle

Okumura, Katsuhiko ; Kita, Tomoko ; Chikazawa, Shinji ; Komada, Fusao ; Iwakawa, Seigo ; Tanigawara, Yusuke. / Genotyping of N-acetylation polymorphism and correlation with procainamide metabolism. In: Clinical Pharmacology and Therapeutics. 1997 ; Vol. 61, No. 5. pp. 509-517.
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