[The acetylator polymorphism in a Khmer population: clinical consequences].
The great variability of slow acetylator (SA) and/or rapid acetylator (RA) frequency is mainly due to ethnic-racial origin. Using the urinary elimination ratio of three metabolites of caffeine--acetylamino formylamino methyluracil (AFMU) to AFMU + 1-methyl urate (1U) + 1-methyl xanthine (1X)--we settled the acetylation phenotype in 54 independent subjects of Khmer and 70 independent subjects of Caucasian origin. Using DNA from peripheral leucocytes, we determined by PCR, in 32 Khmer and 122 Caucasian subjects, the frequencies of wild-type alleles (NAT-2 *4) and of mutated alleles (NAT-2 *5A, *6A, *7A). The frequency of SA was respectively 28 per cent and 61 per cent in Khmer and Caucasian subjects. The antimode of the distribution of the ratio was different in the two populations: 0.07 in Khmers and 0.18 in Caucasians showing a reduced acetylation capacity in the Khmer population in spite of a higher frequency of RA. The frequencies of alleles were also different between the two populations. Between Khmers and Caucasians respectively: *4: 48.4-23.8 per cent *5A: 15.6-44.2 per cent. *6A: 29.7-32.0 per cent. *7A: 6.3-0 per cent. These differences might be taken into account to define a therapeutic strategy in the treatment of tuberculosis by isoniazide.
Bechtel
Y C
YC
Pharmacolgie Clinique, Faculté de Médecine de Besançon, Place St Jacques, 25030 Besançon, France.
Bechtel
P R
PR
Lelouët
H
H
Choisy
H
H
Dy
N R
NR
D000107:Acetylation; D000483:Alleles; D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D001711:Biotransformation / Q000235:genetics; D002110:Caffeine / Q000493:pharmacokinetics; D002160:Cambodia; D002273:Carcinogens / Q000493:pharmacokinetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004252:DNA Mutational Analysis; D004351:Drug Resistance / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D007538:Isoniazid / Q000493:pharmacokinetics / Q000627:therapeutic use; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014376:Tuberculosis / Q000188:drug therapy; D014498:Uracil / Q000031:analogs & derivatives* / Q000652:urine; D014527:Uric Acid / Q000031:analogs & derivatives* / Q000652:urine; D044465:White People / Q000235:genetics; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000652:urine
D000995:Antitubercular Agents; D002273:Carcinogens; D006571:Heterocyclic Compounds; D014970:Xanthines; D014527:Uric Acid; C030530:1-methyluric acid; D002110:Caffeine; D014498:Uracil; C053085:1-methylxanthine; C036692:5-acetylamino-6-formylamino-3-methyluracil; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase; D007538:Isoniazid