In standard microarrays, the probes are attached to a solid surface by a covalent bond to a chemical matrix (via epoxy-silane, amino-silane, NVP-LDE225 lysine, polyacrylamide or others). DNA microarrays can be used to measure changes in gene expression levels to detect SNPs in genotyping or in resequencing mutant genomes [97]. The applicability of microarrays in genomics research has expanded with the evolution and maturation of the technology, but a major issue concerning these methods is still represented by complex data analysis and bioinformatics [98]. In fact, during the last few years, many bioinformatics approaches have been developed to

identify more clearly the genetic/genomic bases of complex and polygenic diseases. Traditionally, this objective has been reached by measuring expression levels of thousands of genes buy FK866 simultaneously and identifying, through different statistical algorithms (e.g. t-tests, non-parametric tests, Bayesian models), those genes expressed differentially among two or more different phenotypic conditions. However, it now well known that results obtained by these methodologies are, most of the time, over-optimistic and poorly reproducible. In addition, it has been demonstrated extensively

that pathway analysis rather than single gene evaluation has many advantages. In a recent paper, Abatangelo et al.[99] reviewed the main technical aspects of pathway analysis and provided practical advice to perform data analysis more efficiently. Therefore, it seems clear that, in future, researchers involved in pharmacogenomics studies

should combine all available methods (associative, U0126 supplier predictive) to obtain more reliable and reproducible results. However, considerable effort needs to be made to produce simple algorithms and statistical methods to identify easily genes expressed differentially or gene variants relevant to drug therapies. Nephrology researchers have begun to employ these innovative high-throughput procedures to identify the whole basal expression profile of normal or pathological human kidney [100], to select biomarkers predicting acute and chronic allograft outcomes [101,102] and to assess more clearly the intricate molecular pathways associated to the pathogenesis and onset of several immunological renal diseases [103,104]. On the contrary, only few reports to date have been published describing the multi-genetic influence on drug response in nephrology. Recently, our group, applying a classical pharmacogenomic approach, has identified a new potential therapeutic target responsible for MPA anti-fibrotic and anti-proteinuric effects. Microarray analysis has revealed that neutral endopeptidase (NEP), a gene encoding for an enzyme involved primarily in the degradation of angiotensin-II, was the most significant up-regulated gene in a cohort of stable renal transplant recipients 3 months after conversion from AZA to MPA.