Pharmacogenetics

Wendell W. Weber, Ph.D., M.D., is Professor at the Pharmacology department at the University of Michigan, Ann Arbor. His teaching and research interests have been concentrated in the area of pharmacogenetics for the past 20 years.

PART I. PHARMACOGENETIC CONCEPTS; CHAPTER 1. BEGINNINGS; 1. The case for pharmacogenetics; 2. Historical perspective; 3. The emergence of pharmacogenetics; 4. The scope of pharmacogenetic variation; 5. The rationale, aims, and significance of pharmacogenetics; 6. Summing up; 7. Note and references; CHAPTER 2. HUMAN DRUG RESPONSE; 1. Introduction; 2. The pharmacologic profile of human drug response; 3. Exploring the pharmacology of human variation in drug response; 4. Drug dose-response relationships in pharmacogenetics; 5. Pharmacologic mechanisms of human drug response; 6. Summing up; 7. Notes and references; CHAPTER 3. HEREDITY; 1. Introduction; 2. The genetic profile of human drug response; 3. Quantitating phenotypic resemblance in relatives of different degrees; 4. Estimating heritability from twin studies; 5. Twin studies in pharmacogenetics; 6. Basic patterns of human inheritance; 7. Mathematical treatment of heterogeneity in human drug response; 8. Testing pharmacogenetic hypotheses with the Hardy-Weinberg law; 9. Some problems in pharmacogenetic investigation; 10. Summing up; 11. Note and references; CHAPTER 4. DRUGS AND GENES; 1. Some general features of the human genome; 2. Genes and the genetic code; 3. Gene regulation; 4. Gene cloning and recombinant DNA; 5. DNA polymorphism; 6. Molecular pharmacogenetics; 7. Summing up; 8. Notes and references; CHAPTER 5. EXPERIMENTAL MODELS; 1. Introduction; 2. Spontaneous mutants in domestic and laboratory species as models of human disease; 3. Mice as models for hereditary mammalian traits; 4. Recombinant, congenic and recombinant congenic mouse strains; 5. Mouse models of arylhydrocarbon and N-acetyltransferase polymorphisms; 6. Mouse models crated by random mutagenesis and gene targeting; 7. Mouse models of human disorders created by gene targeting; 8. Analysis of polygenic traits by systematic quantitative trait loci mapping in mice and rats; 9. Summing up; 10. Notes and references; PART II. APPLICATIONS OF PHARMACOGENETICS; CHAPTER 6. HUMAN DRUG METABOLIZING ENZYME VARIANTS; 1. Introduction; 2. Alcohol intolerance and alcohol metabolism; 3. Cyclophosphamide polymorphism; 4. Dihydropyrimidine dehydrogenase deficiency; 5. Glucose-6-phosphate dehydrogenase deficiency; 6. CYP2C19 (mephenytoin) polymorphism; 7. CYP2D6 (debrisoquin) polymorphism; 8. Paraoxonase polymorphism; 9. Serum cholinesterase sensitivity; 10. Fish odor syndrome; 11. Acetylation polymorphism; 12. Glucuronosyl transferase deficiency; 13. Glutathione transferase deficiency; 14. Thiopurine methyltransferase deficiency; CHAPTER 7. HUMAN NON-DRUG-METABOLIZING ENZYME VARIANTS; 1. Alpha-1-Antitrypsin deficiency; 2. Glucocorticoid remediable hypertension (11-beta-OHSD); 3. Licorice-induced pseudaldosteronism; 4. Pyridoxine deficiency anemia; 5. Intolerance to fructose and lactose; CHAPTER 8. HUMAN DRUG RECEPTOR VARIANTS; 1. Introduction; 2. Cystic fibrosis; 3. Insulin resistance; 4. Malignant hyperthermia; 5. Rhodopsin variants and retinitis pigmentosa; 6. Vasopressin resistance; 7. Antiandrogens and prostate cancer; 8. Estrogen resistance; CHAPTER 9. STRUCTURALLY VARIANT UNIDENTIFIED HUMAN PROTEINS OF PHARMACOGENETIC IMPORTANCE; 1. Aminoglycoside induced deafness; 2. Beryllium-induced lung disease; 3. Coumarin anticoagulant resistance; 4. Hepatitis vaccine resistance; 5. Long QT syndrome; 6. Retinoic acid resistance and acute promyelocytic leukemia; 7. Steroid-induced glaucoma; 8. Thrombophilia (APC resistance); POSTSCRIPT; LIST OF TABLES; LIST OF FIGURES; ADDITIONAL READINGS