Acetylator phenotypes in Papua New Guinea.

Several drugs, including isonicotinyl hydrazide (isoniazid), diamino diphenyl sulphone (dapsone), hydralazine, and some sulphonamides, are metabolised by the liver enzyme acetyl transferase. There is individual variation in the rate at which acetylation occurs and two phenotypes, rapid and slow, are usually recognised, which show an autosomal dominant mode of inheritance. The rapid phenotype includes subjects homozygous and heterozygous for an allele which determines a rapid rate of acetylation. The slow phenotype comprises subjects homozygous for an allele which determines slow acetylation of these drugs. Populations vary in the frequency of rapid and slow acetylators; for instance, the incidence of the slow type may be as low as 5 to 10% in Japanese and Eskimos but up to about 60% in some European, African, and Asiatic Indian populations.1-3 This paper describes the investigation of the acetylator status of 139 Papua New Guineans carried out during a 10-week period of laboratory and field work. Our objective was to assess the population incidence of the acetylator phenotypes in a hitherto untested population, and to evaluate the relevance of the phenotypes in the control of tuberculosis. The acetylator polymorphism is relevant in as much as isoniazid, in combination with other drugs, is the mainstay of antituberculous therapy in PapuaNew Guinea, as in other parts ofthe world. Slow acetylators are more likely to develop peripheral neuropathy on prolonged treatment with isoniazid,4 though this is preventable by pyridoxine supplementation, and rapid acetylators respond less well to a once weekly antituberculous regimen of isoniazid and companion drugs.1 5-7