The Use of DNA Microarray in the Pharmacogenetics of Antidepressants: Guidelines for a Targeted Approach

Recently, microarray technology is reshaping the molecular biology, given the high number of fields of application like, gene expression analysis, rapid sequencing of DNA, mapping of allelic variation, identification polymorphisms. It is a recently developed technique, which allows analysing thousands of genes in a very short time. Due to the powerful nature of this genetic approach, the number of researches using microarray technology boosted in the last years (less than ten papers from 1995 to 1997, up to approximately one thousand in the following 5 years -PubMed). Nevertheless, in spite of the promising fields of application, many drawbacks need to be carefully considered before generalizing the results obtained with this new technology. In fact, up to now a number of drawbacks have been described in the use of DNA microarray: many errors of incorporation during the manufacturing of the chips, loss of splicing variants, variable reliability of differential expression data, low specificity of cDNA microarray probes, discrepancy in fold change calculation for a given gene and so on. In spite of all those troubles, there is no doubt that this new promising technology could give an overall idea of gene organization and expression and might contribute to understanding the molecular mechanisms involved in processes as disease diagnosis or drug discovery (Pharmacogenetics and Pharmacogenomics). The goal of the present review is to suggest a targeted use of DNA chip technology in the field of pharmacogenetics (with the example of antidepressants), suggesting the inclusion of only those genes, possibly candidates, through a step by step analysis of the pathways involved in the pharmacological action of antidepressants.