The relationship between the acetylator and the sparteine hydroxylation polymorphisms.

Thirty-eight healthy white British Caucasian subjects were hydroxylator phenotyped with sparteine and acetylator phenotyped with sulphadimidine. The results showed that there was no significant difference in the mean sparteine metabolic ratio between eight rapid acetylator extensive hydroxylators and 27 slow acetylator extensive hydroxylators.

Polymorphic hydroxylation of perhexiline maleate in man.

Long term perhexiline maleate therapy causes peripheral neuropathy and hepatic damage in certain subjects. An association between these adverse reactions and a genetically determined relative inability to hydroxylate debrisoquine has been described. This association could indicate either that the effects of perhexiline impair debrisoquine oxidation thus producing a phenocopy, or that perhexiline is polymorphically hydroxylated and that the polymorphism is controlled by the same alleles as control the debrisoquine polymorphism.

The association of the slow acetylator phenotype with bladder cancer.

There is an association between exposure to aromatic amines and the development of bladder cancer. Aromatic amines such as are known to occur in tobacco smoke are polymorphically acetylated. One hundred bladder cancer patients have been acetylator phenotyped.

The genetic control of sparteine and debrisoquine metabolism in man with new methods of analysing bimodal distributions.

Debrisoquine and sparteine tests were carried out in 215 random white British subjects. There is a high degree of correlation between the urinary 'metabolic ratios' of the two drugs. New mathematical techniques have been developed (1) to define phenotypes and (2) to identify the genotypes within the dominant phenotype.