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Interethnic differences in cytochrome P450 polymorphism might be responsible, at least in part, for the variations in drug disposition between ethnic groups. Of the various CYP2C9 alleles, CYP2C9*2 and CYP2C9*3 have been reported to have altered catalytic activities compared to the wild-type CYP2C9*1. The present study is aimed at analysing the CYP2C9 polymorphism in a Mexican-American compared with a Spanish population. Differences between the two populations of healthy volunteers, Mexican-Americans (n=98 subjects) and Spaniards (n=102 subjects), regarding the CYP2C9 allele frequencies have been found. CYP2C9 genotypes among the studied Mexican-American population are in equilibrium. The 95%CI were, respectively, 0.81-0.90 for CYP2C9*1 (n=169), 0.05-0.13 for CYP2C9*2 (n=16) and 0.031-0.10 for CYP2C9*3 (n=11). CYP2C9*4,*5 and*6 were found in none of the studied subjects. The frequency of CYP2C9*2 was lower among Mexican-Americans compared to Spaniards (P<0.05). The obtained frequency of CYP2C9 alleles is compatible with the genomic assembly of the constitutive potential ethnic origin of this population, and supports the need of pharmacogenetic studies for optimizing the recommended drug dosages to Mexican-Americans.The Pharmacogenomics Journal (2004) 4, 403-406. doi:10.1038/sj.tpj.6500278 Published online 28 September 2004 [ABSTRACT FROM AUTHOR]

Both the prototypic tricyclic antidepressant imipramine (IMI) and the herbal product St John's wort (SJW) can be effective in the treatment of major depressive disorder. We studied hypothalamic gene expression in rats treated with SJW or IMI to test the hypothesis that chronic antidepressant treatment by various classes of drugs results in shared patterns of gene expression that may underlie their therapeutic effects. Individual hypothalami were hybridized to individual Affymetrix chips; we studied three arrays per group treatment. We constructed 95% confidence intervals for expression fold change for genes present in at least one treatment condition and we considered genes to be differentially expressed if they had a confidence interval excluding 1 (or -1) and had absolute difference in expression value of 10 or greater. SJW treatment differentially regulated 66 genes and expression sequence tags (ESTs) and IMI treatment differentially regulated 74 genes and ESTs. We found six common transcripts in response to both treatments. The likelihood of this occurring by chance is 1.14 × 10-23. These transcripts are relevant to two molecular machines, namely the ribosomes and microtubules, and one cellular organelle, the mitochondria. Both treatments also affected different genes that are part of the same cell function processes, such as glycolytic pathways and synaptic function. We identified single-nucleotide polymorphisms in the human orthologs of genes regulated both treatments, as those genes may be novel candidates for pharmacogenetic studies. Our data support the hypothesis that chronic antidepressant treatment by drugs of various classes may result in a common, final pathway of changes in gene expression in a discrete brain region.Molecular Psychiatry (2004) 9, 237-251. doi:10.1038/sj.mp.4001470 Published online 13 January 2004 [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses articles on pharmacogenomics of antidepressants, development of pharmacogenomics from human genome, and development of targeted therapeutics based on molecular understanding of pathogenesis.

Discusses the genomics aspects of pharmacogenomics research. Study of single nucleotide polymorphism in candidate genes; Statistical approaches in pharmacogenomics research; Study of genotyping.

Discusses clinical issues concerning pharmacogenomics in psychiatry. Correct assignment of phenotypes; Environmental contributions to treatment outcome, excessive expectations, confidentiality, and community consultation and engagement; Treatment compliance; Need to differentiate placebo from drug responders within the drug-treated group.

Editorial. Focuses on the role of pharmacogenomics in adverse drug reactions. Evidence supporting the role of pharmacogenomics in adverse drug reactions; Overview of a study on the use of pharmacogenomic strategy to predict liver toxicity; Significance of pharmacogenomics research.

Editorial. Introduces a series of articles which explores the relevance of the science of complexity to pharmacogenomics.

Editorial. Discusses whether pharmacogenomics guides clinical practice. Details on pharmacogenomics; Specific case of inadequate translation of research into clinical medicine; Reasons there is a disconnect between research and clinical practice in pharmacogenomics.