Interethnic difference

Nakamura, K., Goto, F., Ray, W. A. etal. (1985). Interethnic differences in genetic polymorphism of debrisoquine and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin. Pharmacol. Ther., 10,402-8. 

Tab. 8.3 Interethnic differences in allele and genotype frequencies of the MDR7 exon 26 C3435T polymorphism...

Klemetsdal B, Tollefsen E, Loenne-chen T, Johnsen K, Utsi E, Gisholt K, Wist E, Aarbaake J. Interethnic differ-... 

T. L. Diepgen, M. Geldmacher-von Mallinckrodt, Interethnic Differences in the Detoxification of Organophosphates The Human Serum Paraoxonase Polymorphism , Arch. Toxicol. 1986, Suppl. 9, 154-158. 

Closer to the target of clinical effects are data obtained in humans. Here of course the problem of interspecies differences is avoided, but other problems become foremost. One of these is genetic differences between humans, with the discovery of genetic polymorphism in enzymes (Meyer et al., 1990) and receptors (Strange, 1994). Ethnopharmacology was born with the discovery that variations in genotypes and phenotypes between human populations are observed that cause many interethnic differences in drug responses (Kalow and Bertilsson, 1994). 

The deficiency of debrisoquine metabolism (19) was also tested in our laboratory, and we found a different metabolic ratio between Chinese and Caucasian students (34). These observations, together with the old G6PD and NAT2 data and some additional comparisons, firmly planted in my mind the idea that differences in drug metabolism are not only a matter of individuals but frequently occur also between the human populations. I published a review article that probably was the first exclusively concerned with interethnic differences of drug metabolism (35). Knowledge of such differences has become very important for the pharmaceutical industry. 

Yue Q, Sawe K. Interindividual and interethnic differences in codeine metabolism. In Kalow W, ed. Pharmacogenetics of Drug Metabolism. New York Pergamon Press, 1992 721-727. 

Bertilsson L, Kalow W. Interethnic differences in drug disposition and effects. In Pacifici GM, Pelkonen O, eds. Interindividual Variability in Human Drug Metabolism. London New York Taylor Francis, 2001 15-74. 

Attention to interethnic differences has become a major aspect of pharmacogenetics (1-9) stimulated by studies of drug response and toxicity in various human populations who differed in their response, even when taking usually well tolerated doses of some common therapeutic chemicals. The purpose of this chapter is to indicate essential elements of this broad topic, and to provide examples of some of its important aspects. 

Thus, while most interethnic differences in drug response are now known to have a genetic basis, it would be wrong to assume automatically that there must be a genetic cause. 

In short, the interethnic differences in the structure of ADH appear to have sufficient effects upon the fate of ethanol to be one of the determinants of alcoholism. Furthermore, one should not exclude the possibility that variation of ADH matters, for the fate of endogenous (89,90) or exogenous substrates (91,92). Ethanol is also metabolized by CYP2E1, but this enzyme is quantitatively less important than are the ADH (93). 

Whenever inter-individual pharmacogenetic differences are observed, a proper search usually showed the existence of equivalent interethnic differences. It is not entirely clear whether this rule applies specifically to pharmacogenetics, or whether it affects all genetic variations to the same extent. 

Kalow W. Interethnic differences in drug response. In Kalow W, Meyer UA, Tyndale R, eds. Pharmacogenomics. New York, Basel Marcel Dekker Inc., 2001 109-134. 

Typically, this type of evaluation would be extended during later clinical development by performing a population pharmacokinetic/pharmacodynamic assessment of the impact of genetically determined (interethnic) differences on the disposition of the developmental drug during the phase II/III studies. 

As expected, homozygous PM subjects have lower metabolic activity as compared to heterozygous PM subjects, and potential interethnic difference has been noticed within a genotype (Yin 2004). 

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