ABSTRACT
Pharmacogenetics deals with pharmacological responses and their modification by hereditary influences”. This definition, offered by Werner Kalow in the first book dedicated to pharmacogenetics,1 highlights the three pillars of this discipline: phar macology, genetics and human diversity. Pharmacogenetics has evolved greatly over the 50
years elapsed since Kalow's book was published, was rechristened as pharmacogenomics in the fashion of the “omics” revolution, but its conceptual development and praxis remain contingent upon a better understanding of human genomic diversity and its impact on drug pharmacokinetics and pharmacodynamics. The evolution and structure of human genetic diversity has been reviewed in this book by Sergio Pena (Chapter 2),2 who pre sented three models: The first, essentially typological, is based on the partition of humanity into races, visualized as being very different from each other, but internally homogeneous; the second, proposes a division into (continental) populations rather than races; the third, labeled the variable mosaic genome-VMG-paradigm, stresses individuality rather than mem bership in population categories based on race, ethnicity or geographical origin.2 I would suggest that most pharmacogenetics/-genomics (PGx) studies continue to be performed, and their data analyzed, reported and fed into databases, in consonance with either the first or the second models described by Pena.2 A caveat with this approach is that either model is a poor descriptor of admixed populations-which are the focus of this booksince genetic admixture is best modeled as a continuous variable, consistent with the VGM paradigm.2,3 The individual uniqueness that is central to this paradigm implies that ‘each person must be treated as an individual, rather than as an exemplar of a race”4 or in the words of Howard McLeod (Chapter 4),5 “data from ethnic groups will not be as useful as analysis o f individuals patients. While knowledge of ethnic differences may be relevant to much of the w orld 's population, its usefulness is significantly lim ited in situations of extensive genetic mixing”. Rashmi Shah (Chapter 12)6 predicts that “with increasing global migration and the resulting admixing of different ethnic populations, the challenge in the future will be even greater”.
