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5 - Pharmacogenetics of ethnic populations

Published online by Cambridge University Press:  22 August 2009

By
Min-Soo Lee ,
Rhee-Hun Kang  and
Sang-Woo Hahn
Edited by
Chee H. Ng ,
Keh-Ming Lin ,
Bruce S. Singh  and
Edmond Y. K. Chiu
Min-Soo Lee
Affiliation:
Department of Psychiatry, Korea University College of Medicine, Seoul, Korea
Rhee-Hun Kang
Affiliation:
Department of Psychiatry, College of Medicine, Korea University, Seoul, Korea
Sang-Woo Hahn
Affiliation:
Department of Psychiatry, College of Medicine, Soonchunhyang University, Seoul, Korea
Chee H. Ng
Affiliation:
University of Melbourne
Keh-Ming Lin
Affiliation:
National Health Research Institutes, Taiwan
Bruce S. Singh
Affiliation:
University of Melbourne
Edmond Y. K. Chiu
Affiliation:
University of Melbourne
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Summary

Introduction

Highly complex mechanisms underlie the variability in drug responses, which can be attributed to several physiological and environmental factors such as age, renal and liver function, nutritional status, smoking, and alcohol consumption. However, it has been established for almost half a century that genetic factors also influence both the efficacy of a drug and the likelihood of adverse reactions (Weinshilboum, 2003). Psychotropic drugs appear to be effective across cultures and ethnicities (Lin, Poland & Nakasaki, 1993, Lin, Tsai, Yu et al. 1999), but it is increasingly recognized that these responses also vary (Lin & Poland, 1995; Poolsup, Li Wan Po & Knight 2000). The discovery of widespread ethnospecific polymorphisms in genes governing pharmacokinetic and pharmacodynamic aspects of psychotropic drugs may explain some of these variations (Lin et al., 1999; Kalow, 1992).

Pharmacodynamic aspects

The term pharmacodynamics encompasses all the processes that influence the relationship between drug concentration and resulting effects. Psychotropic drugs have a wide variety of targets within neurotransmitter systems, including neurotransmitter synthesis, degradation of enzymes, storage, receptors, and specific transporter proteins.

Genetic studies of antidepressants

Serotonin transporter

The brain 5-HT transporter (5-HTT) is the principal site of action of many antidepressants. This transporter takes up 5-HT into the presynaptic neuron, thus terminating synaptic actions, and recycles it into the neurotransmitter pool. Ramamoorthy, Bauman, Moore et al. (1993) identified and cloned a single gene encoding the human 5-HTT, localized to chromosome 17q11.1∼q12, spanning 21 kb, and consisting of 14 exons (Lesch, Balling, Gross et al., 1994).

Type
Chapter
Information
Ethno-psychopharmacology
Advances in Current Practice
 , pp. 62 - 86
Publisher: Cambridge University Press
Print publication year: 2008

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