Pharmacogenetics

In recent years, we have been increasingly engaged in pharmacogenetic research. Pharmacogenetics is a branch of pharmacology that studies how individual genetic variations influence drug response. At the core of this science lies the understanding that each individual has a unique genetic profile, which can lead to significant differences in the efficacy and safety of pharmacological treatments. This awareness has marked a turning point in the traditional therapeutic paradigm, paving the way for personalized medicine.

The main goal of pharmacogenetics is to optimize therapies by identifying in advance the patients who are most likely to respond well to a given drug, those at risk of serious side effects, or those for whom the treatment would be ineffective. This approach is based on the analysis of genes involved in pharmacokinetic processes (absorption, distribution, metabolism, and elimination of drugs) and pharmacodynamic mechanisms (interaction of the drug with its biological target). One of the most well-known examples is the CYP2D6 gene, which encodes a liver enzyme involved in the metabolism of numerous drugs, including antidepressants, antipsychotics, and opioid analgesics such as tramadol and codeine. Genetic variants of this gene can result in absent, reduced, normal, or ultra-rapid enzyme activity, directly affecting plasma drug levels and, consequently, the patient’s clinical response. For example, in poor metabolizers, a standard dose may lead to accumulation and toxicity, whereas in ultra-rapid metabolizers, the same drug might be ineffective due to insufficient active concentration.

Other relevant genes include TPMT (thiopurine methyltransferase), essential for metabolizing thiopurines used in oncology and autoimmune diseases, and HLA-B*57:01, whose presence is associated with severe hypersensitivity reactions to the antiretroviral drug abacavir. Pharmacogenetics has demonstrated significant clinical applications in oncology, cardiology, psychiatry, and neurology. In oncology, for example, predictive genetic testing helps select targeted treatments based on tumor mutations, while also assessing the patient’s genetic profile to avoid serious toxicities—such as in the case of the DPYD gene, whose mutation is associated with high toxicity risk from fluoropyrimidines (5-FU, capecitabine). Another fundamental aspect is the interindividual variability related to sex: men and women may express certain key metabolic enzymes, such as cytochromes, differently, with clinically significant consequences. This highlights how pharmacogenetics must be integrated with other parameters—such as sex, age, hormonal status, comorbidities, and polypharmacy—for truly personalized care.

Despite its potential, the routine application of pharmacogenetics still faces challenges, including limited training among healthcare professionals and the lack of standardized guidelines for each clinical context. However, advances in genomics, the decreasing costs of sequencing technologies, and the growing focus on precision medicine are progressively addressing these gaps.

Pharmacogenetics therefore represents a strategic frontier of modern medicine: not just treating disease, but caring for the individual in their unique genetic and biological identity. It is a step forward toward more effective, safer, and ethically responsible medicine—one to which our laboratory is committed to contributing.