ABSTRACT
The essence of the molecular basis of pharmacogenetics is best illustrated by some examples from the animal kingdom. The great majority of congenital malformations are due to interplay of genetic and nongenetic factors. Mice of strain C3H were described as being particularly resistant to histamine. The best example of drug resistance is insulin resistance in mice of the KL strain. Most mice tolerate only three to eight units of insulin; obese mice with hereditary diabetes tolerate 20 units, whereas mice of the KL strain survive after 300 to 500 units. In humans the most spectacular example is the prolonged action of succinylcholine in patients with atypical pseudocholinesterase. The drugs nitrite and p-aminopropiophenone form methemoglobin in patients with hereditary methemoglobinemia in different ways—nitrite quickly and steichiometrically, and p-aminopropiophenone slowly and catalytically. Reduction of methemoglobin to hemoglobin occurs through four metabolic pathways: NADH-and NADH-dependent reducing pathways, and direct reducing pathways involving ascorbic acid and reduced glutathione.
