Arxiu d'etiquetes: polymorphism

Pharmacogenetics: a drug for each person

Sometimes, some people say that the medications prescribed by doctors are not good. Can this be true? Not all drugs work for the same population. Keep reading and discover the secrets of pharmacogenetics.


The same that happens with nutrients, happens with drugs. Another objective of personalized medicine is to make us see that not all medicines are for everyone. However, it does not come again because around 1900, the Canadian physician William Osler recognized that there was an intrinsic and specific variability of everyone, so that each one reacts differently to a drug. This is how, years later, we would define pharmacogenetics.

It is important to point out that it is not the same as pharmacogenomics, which studies the molecular and genetic bases of diseases to develop new treatment routes.

First, we need to start at the beginning: what is a drug? Well, a drug is any physicochemical substance that interacts with the body and modifies it, to try to cure, prevent or diagnose a disease. It is important to know that drugs regulate functions that our cells do, but they are not capable of creating new functions.

Apart from knowing if a drug is good or not for a person, you also have to take into account the amount that should be administered. And we still do not know the origin of all diseases, that is, we do not know most of the real molecular and genetic causes of diseases.

The classification of diseases is based mainly on symptoms and signs and not on molecular causes. Sometimes, the same group of pathologies is grouped, but among them there is a very different molecular basis. This means that the therapeutic efficacy is limited and low. Faced with drugs, we can manifest a response, a partial response, that produces no effect or that the effect is toxic (Figure 1).

efectivitat i toxicitat
Figure 1. Drug toxicity. Different colours show possible responses (green: drug not toxic and beneficial; blue: drug not toxic and not beneficial; red: drug toxic but not beneficial; yellow: drug toxic but beneficial) (Source: Mireia Ramos, All You Need is Biology)


Drugs usually make the same journey through our body. When we take a drug, usually through the digestive tract, it is absorbed by our body and goes to the bloodstream. The blood distributes it to the target tissues where it must take effect. In this case we talk about active drug (Figure 2). But this is not always the case, but sometimes it needs to be activated. That’s when we talk about a prodrug, which needs to stop in the liver before it reaches the bloodstream.

Most of the time, the drug we ingest is active and does not need to visit the liver.

active and prodrug
Figure 2. Difference between prodrug and active drug (Source: Agent of Chemistry – Roger Tam)

Once the drug has already gone to the target tissue and has interacted with target cells, drug waste is produced. These wastes continue to circulate in the blood to the liver, which metabolizes them to be expelled through one of the two routes of expulsion: (i) bile and excretion together with the excrement or (ii) purification of the blood by the kidneys and the urine.


A clear example of how according to the polymorphisms of the population there will be different response variability we find in the transporter genes. P glycoprotein is a protein located in the cell membrane, which acts as a pump for the expulsion of xenobiotics to the outside of the cell, that is, all chemical compounds that are not part of the composition of living organisms.

Humans present a polymorphism that has been very studied. Depending on the polymorphism that everyone possesses, the transporter protein will have normal, intermediate or low activity.

In a normal situation, the transporter protein produces a high excretion of the drug. In this case, the person is a carrier of the CC allele (two cytokines). But if you only have one cytosine, combined with one thymine (both are pyrimidine bases), the expression of the gene is not as good, and the expulsion activity is lower, giving an intermediate situation. In contrast, if a person has two thymines (TT), the expression of the P glycoprotein in the cell membrane will be low. This will suppose a smaller activity of the responsible gene and, consequently, greater absorption in blood since the drug is not excreted. This polymorphism, the TT polymorphism, is dangerous for the patient, since it passes a lot of drug to the blood, being toxic for the patient. Therefore, if the patient is TT the dose will have to be lower.

This example shows us that knowing the genome of each individual and how their genetic code acts based on it, we can know if the administration of a drug to an individual will be appropriate or not. And based on this, we can prescribe another medication that is better suited to this person’s genetics.


The applications of these disciplines of precision medicine are many. Among them are optimizing the dose, choosing the right drug, giving a prognosis of the patient, diagnosing them, applying gene therapy, monitoring the progress of a person, developing new drugs and predicting possible adverse responses.

The advances that have taken place in genomics, the design of drugs, therapies and diagnostics for different pathologies, have advanced markedly in recent years, and have given way to the birth of a medicine more adapted to the characteristics of each patient. We are, therefore, on the threshold of a new way of understanding diseases and medicine.

And this occurs at a time when you want to leave behind the world of patients who, in the face of illness or discomfort, are treated and diagnosed in the same way. By routine, they are prescribed the same medications and doses. For this reason, the need has arisen for a scientific alternative that, based on the genetic code, offers to treat the patient individually.


  • Goldstein, DB et al. (2003) Pharmacogenetics goes genomic. Nature Review Genetics 4:937-947
  • Roden, DM et al. (2002) The genetic basis of variability in drug responses. Nature Reviews Drug Discovery 1:37-44
  • Wang, L (2010) Pharmacogenomics: a system approach. Syst Biol Med 2:3-22
  • Ramos, M. et al. (2017) El código genético, el secreto de la vida. RBA Libros
  • Main picture: Duke Center for Applied Genomics & Precision Medicine



Nutritional genomics: À la carte menu

When Hipprocrates said “let food be your medicine and medicine be your food” he knew that food influences our health. And it tells us that nutritional genomics, which I will discuss in this article; a new science appeared in the post genomic era as a result of the sequencing of human genome (all DNA sequences that characterize an individual) and the technological advances that allow the analysis of large amounts of complex information.   


The aim of nutritional genomics is to study the interactions of genes with elements of the human diet, altering cellular metabolism and generating changes in the metabolic profiles that may be associated with susceptibility and risk of developing diseases.

This study wants to improve the health and to prevent diseases based on changes in nutrition. It is very important not understand nutritional genomics how that specific food or nutrients cause a particular answer to certain genes.

When we talk about diet we have to distinguish between what are nutrients and what are food. Nutrients are compounds that form part of our body, while foods are what we eat. Food can take many nutrients or only one (such as salt).


Within nutritional genomics we find nutrigenomics and nutrigenetics, but although their names we may seem to mean the same is not the case (Figure 1).

Nutrigenomics is the study of how foods affect our genes, and nutrigenetics is the study of how individual genetic differences can affect the way we respond to nutrients in the foods we eat.

Figure 1. Schematic representation of the difference between nutrigenomics and nutrigenetics (Source: Mireia Ramos, All You Need is Biology)


Nutrients can affect metabolic pathways and homeostasis (balance) of our body. If this balance is disturbed chronic diseases or cancer may appear, but it can also happen that a disease, which we have it, be more or less severe. It means that impaired balance can give the appearance, progression or severity of diseases.

The aim of nutrigenomics is that homeostasis is not broken and to discover the optimal diet within a range of nutritional alternatives.

Thus, it avoids alterations in genome, in epigenome and/or in expression of genes.


Free radicals are subproducts that oxidise lipids, proteins or DNA. These can be generated in mitochondria, organelles that we have inside cells and produce energy; but we can also incorporate from external agents (tobacco, alcohol, food, chemicals, radiation).

In adequate amounts they provide us benefits, but too much free radicals are toxic (they can cause death of our cells).

Antioxidants neutralize free radicals. But where can we get these antioxidants? There are foods that contain them, as Table 1 shows.

Table 1. Example of antioxidants and some foods where we can find them (Source: ZonaDiet)

The way we cook food or cooking is important for avoid to generate free radicals. In barbecues, when we put the meat on high heat, fats and meat juices fall causing fire flames. This produces more flame and it generates PAHs (a type of free radicals). These adhere to the surface of the meat and when we eat it can damage our DNA.


Epigenome is the global epigenetic information of an organism, ie, changes in gene expression that are inheritable, but they are not due to a change in DNA sequence.

Epigenetic changes may depend on diet, aging or drugs. These changes would not have to exist lead to diseases as cancer, autoimmune diseases, diabetes…

For example, with hypomethylation, in general, cytosines would have to be methylated are not. What does it mean? Hypomethylation silenced genes and then, they cannot be expressed. Therefore, we need methylated DNA. A way of methylate DNA is eating food rich in folic acid.


There are agents (UV rays) that activate pathways that affect gene expression. Occurring a cascade that activates genes related to cell proliferation, no differentiation of cells and that cells survive when they should die. All this will lead us cancer.

It has been found that there are foods which, by its components, can counteract activation of these pathways, preventing signal transduction is given. For example curcumin (curry), EGCG (green tea) or resveratrol (red wine).