CNIO researchers analyse how the Spanish population responds to common drugs according to their genetics

The study that analyses the impact of genetics among the Spanish population in their response to drugs has just been published by researchers from CNIO (National Cancer Research Centre) in the journal Pharmaceutics. The paper focuses on variants of the 21 genes that play a role in metabolism, transport or are target of the most common drugs.

This research conducts an in-depth analysis of genetic information from 3006 people, a representative sample of the Spanish population. The results indicate that 98% of our population carries at least one pharmacogenetic gene [a relevant gene in drug interaction] with variants that could affect response to treatments.

Practically the entire population “could benefit from the use of this information to personalise their treatment and, consequently, improve the response to it,” says Anna González Neira, head of the Human Genotyping Unit at CNIO and director of the research. “Treatments could be adjusted to find the best fit for each individual according to their pharmacogenetic genes, so that they are more efficient and safer.”

Specifically, 50% of the population would benefit from changes in the usual treatments with tricyclic antidepressants, and 10% from adjustments in certain anticoagulants, antitumour, and immunosuppressants, among other drugs. These changes range from finding an alternative drug to prescribing a different dose to the standard one.

“Our study provides valuable reference information to help implement pharmacogenetic diagnosis in Spain,” adds González Neira.

Preventive testing to determine the pharmacogenetic profile

Pharmacogenetics seeks to offer patients “optimal treatments and move towards personalised medicine,” says González Neira. “Our ultimate goal is to find out, through a single preventive test, the pharmacogenetic profile of each individual in order to personalise the use of as many drugs as possible.”

Adverse drug reactions are “a serious clinical problem,” write the authors of the paper, including the lead author Rocío Núñez Torres from CNIO.

Adverse drug effects are considered the fifth leading cause of death in Spain. One of the factors that contribute to such reactions is human genetic variability: even if a drug is effective for most of the population – which is why it is approved -, it may not be useful, or could even be harmful for people with a certain genetic profile.

Delays in clinical application

In recent years, the increasing abundance of genomic and epidemiological data from different populations, stored in databases accessible to the international scientific community, has furthered the field of pharmacogenetics. But the reality is that “the implementation of pharmacogenetic diagnosis is still extremely slow and uneven around the world,” writes Núñez Torres and her fellow authors in Pharmaceutics.

In order to make it easier for pharmacogenetic knowledge to reach clinical practice, information on the specific genetic variability of each population is essential. For this reason, genomic data were collected from more than 3,000 people (50% men/women) from all over Spain, and the researchers searched for genetic variants of 21 pharmacogenes that affect the response to 64 drugs. It is, say the researchers, the “most complete study [of pharmacogenetics] carried out in the Spanish population to date.

Antidepressants, ibuprofen, simvastatin, tamoxifen and 50 other drugs

The 64 drugs analysed include some as common as simvastatin -used to lower cholesterol-, tricyclic antidepressants, the antitumour drug tamoxifen and the immunosuppressant tacrolimus.

“Our study shows that patients treated with tricyclic antidepressants are the ones who could benefit most from a pharmacogenetic diagnosis, since about 50% of Spaniards would need to be prescribed an alternative drug or a decrease in the initial dose,” write the authors.

In addition, “about a third of the population would need a different prescription for antiretroviral therapy, opioids and some antitumour drugs, such as tamoxifen. The family of non-steroidal anti-inflammatory drugs, such as ibuprofen, simvastatin, anticoagulant therapy with clopidogrel and the immunosuppressant tacrolimus appear to be altered in ~10-20% of the Spanish population,” they add.

Spanish genetic variability in a database

All the information obtained has been made available to the scientific community in the Collaborative Spanish Variability Server (CSVS), a project started three years ago, and which already has more than 2,000 genomes from unrelated Spanish subjects.

In addition, González-Neira adds “Although there are already pharmacogenetic clinical guidelines available to be used in the clinical field, within the Spanish Society of Pharmacogenetics and Pharmacogenomics (SEFF) we are working intensively on the development of specific Spanish guidelines that facilitate and accelerate the implementation of pharmacogenetics in our country.”

The authors are aware, however, that although the study of our genes for the personalisation of treatment provides valuable information, it has to be managed within a clinical context where all the patient’s clinical information (age, sex, other diseases) is available, and possible interactions with other drugs can also be taken into account in the case of polymedicated patients.

Image: Authors of the paper. From left to right: Belén Herráez, Anna González Neira, Rocío Núñez, Charo Alonso, Guillermo Pita y Nuria Álvarez, at Spanish National Cancer Research Center (CNIO). / Laura M. Lombardía. CNIO

Reference article: Nunez-Torres, R.; Pita, G.; Peña-Chilet, M.; López-López, D.; Zamora, J.; Roldán, G.; Herráez, B.; Álvarez, N.; Alonso, M.R.; Dopazo, J.; Gonzalez-Neira, A. A Comprehensive Analysis of 21 Actionable Pharmacogenes in the Spanish Population: From Genetic Characterisation to Clinical Impact. Pharmaceutics 2023, 15, 1286. https://doi.org/10.3390/pharmaceutics15041286