The Pharmacogenetics Unit studies the genetic variability regarding the response to drugs to predict effectiveness and safety of the treatments associated. The subject of analysis are genetic variants present in genes coding for proteins and enzymes of drug transport, metabolism and drug target/mechanism of action.
Amongst the possible genetic variants, this Unit analyzes the Single Nucleotide Polymorphisms (SNPs), which represent 90% of all the human genetic variability, existing approximately 1 SNP every 1.700 nucleotides.
The analyses are performed in the MassArray Compacte © – SEQUENOM genotyping platform, based on PCR followed by Maldi-Tof mass spectroscopy.
This device allows in one single assay the determination of about 40 SNPs, in 40 different samples (patients), running the test in triplicates; that is 1.600 genetic determinations at a time, which allows the inclusion of validated and candidate SNPs in the same design.
The Results Report contains:
- Which genes and SNPs have been analyzed, with the patient’s genotype and the expected frequencies for each genetic variant in the global population.
- Which is the effect of the variant. If this is known, the report will contain the biological meaning or phenotype associated to the variant.
- What should be done to the patient’s pharmacological treatment. If existing, the pharmacological recommendation or the appropriate warnings will be given.
SERVICES AND EXPERTISSE
Service description and Clinical and Research applications:
The Service offered by the Unit is tailored analyses of combinations of SNPs, grouped in different panels, which can also be subdivided into smaller groups in order to help choose the best combination of SNPs for each study. The designs typically contain SNPs already validated by FDA or EMA (if existing), SNPs included in the drug’s label; and SNPs proposed in the literature and PharmGKB consortium to have a relevant role in the drug’s action.
A) The already developed panels are:
- Immunosuppressants (especially those used for solid organ transplantation: renal, heart, liver and lung)
- Adult Oncology: Breast Cancer and Acute Myeloid Leukemia (Colon cancer in development)
- Heart Failure (beta-blockers, ACE inhibitors and aldosterone antagonists)
B) Tailored designs of new panels can be performed: this includes designs regarding pathology, and/or gene, and/or drug; and all of them addressed to translational research or to medical practice.