It’s Too Long for You to Read? Here Is a Summary
The whole idea of this blog post is the following. It introduces and explains that our genes determine how we process our medications. So, depending on genetics, two random individuals can process and react to the same drug differently, even though both have the same condition for which they are treated. This change in reaction to medications is because we carry genetic mutations. These genetic mutations are in genes that encode enzymes that process medications we take, and, therefore, genetic mutations affect the functionality of enzymes in different ways, leading to variations in how we respond to medications.
For example, some individuals might have less or more effective enzymes requiring an adjustment in dosage of the given medication; some medications might have different toxicity levels, causing different adverse effects.
One might say, OK, I got the idea, but this means I have to do complicated genetic testing to determine what kind of genetic mutations I have. Well, yes, that’s true, but also, many people have those 23andMe or AncestryDNA tests done, and that data also contains all that information. You can quickly recover over 1500 gene-drug interactions from 23andMe and AncestryDNA data without testing but just processing that raw genotype data.
OK, if you find this story interesting, keep reading, as this was only a summary of the whole blog post. Keep reading, and I will provide you with all the details.
What Makes All Humans Very Similar Is Our DNA: A Blueprint of Our Bodies, but DNA Is What Makes Us Different as Well
DNA is often called a blueprint for our bodies because DNA contains all information based on which our body is built. How this works is very simple: the building blocks of our body are proteins, and all proteins are encoded by DNA (more precisely, those A, C, T, and G). So, DNA contains information about how proteins will be produced and structured.
So, DNA is the basis of what makes any two individuals different. I would assume that you already know that. Monozygotic twins are exceptions as their DNA is identical.
Still, when we compare DNA between any two individuals on the planet, on average, 99.6% of their DNA will be the same, and the rest of 0.4% will be different. But that small portion of DNA makes us look different, have different hair color, eyes, and many other things, including how we respond to different medications.
So, DNA is what is common for all humans. Still, that small portion of DNA (0.4% on average) that differs between any two individuals (except monozygotic twins) makes any individual unique. Those differences are what we call genetic variants or genetic mutations.
How Do Our Genes Determine How Our Body Responds to Drugs?
OK, In the previous paragraph, I introduced the concept of DNA and how DNA determines our proteins. Proteins are the building blocks of our body. For example, our muscles are built from proteins, and our blood is composed of cells built of proteins, but enzymes are also proteins and essential. These proteins catalyze many chemical reactions happening in our body, starting from digesting our food, helping absorb our digested food, and many other things, including processing medications/drugs we take.
So, medications we use to treat diseases are processed and interact with different enzyme types in our bodies. To remind you, segments of DNA (also known as genes) encode those enzymes, or information contained in DNA is transferred into those proteins. That is why we refer to DNA as the blueprint of our body.
We all have the same genes (segments of DNA), but what makes us different is those minor DNA variations (genetic mutations) I mentioned above that make us different. Those genetic mutations make our genes different, and as a consequence enzymes being encoded by those genes are different. These differences in enzymes from individual to individual is what makes them to have various levels of efficiency and ability to metabolize drugs/medications we are taking. Now, we are ready to present the main part of this post.
Use-Case: How DNA Affects How Our Body Responds to Gliclazide
OK, I hope I was successful in introducing the key concepts. What we learned is the following:
DNA is what makes us similar, but a small portion of DNA, which are genetic mutations, is what makes us different
Genetic mutations make proteins and among proteins enzymes different between different individuals, including how we react to medications.
This means that based on genetic mutations, we can potentially figure out how an individual will respond to a specific drug and use this information to avoid any adverse side effects or improve dosage to have a better effect on the drug.
To illustrate the above stated, I will introduce an example. The example I will use is about gliclazide, the KCNJ11 gene, and how a mutation in the KCNJ11 gene affects how we process gliclazide.
First, let’s break down and explain the main terms in this use case.
What Is Gliclazide?
Gliclazide is a medication primarily used to help lower blood sugar levels in patients with type 2 diabetes. Type 2 diabetes is a disease where the body either does not produce enough insulin or does not use insulin effectively. Insulin is a hormone that helps regulate blood sugar (glucose) levels in the body. Therefore, if the body does not produce enough insulin, the blood sugar level rises, hence the need for medications like gliclazide.
Gliclazide stimulates the pancreas to release more insulin, which further helps lower blood sugar levels by facilitating glucose uptake into cells for energy. Gliclazide is typically prescribed as part of a comprehensive treatment plan for type 2 diabetes, including dietary changes, exercise, and other medications.
Gliclazide: Side-Effects
What you will read about gliclazide is that it is important to note that it should obviously be used under the supervision and guidance of a healthcare professional, as they will determine the appropriate dosage and monitor its effectiveness and any potential side effects.
Gliclazide may not be suitable for everyone, and its use should be tailored to an individual's specific needs and medical history. Common side effects of gliclazide can include low blood sugar (hypoglycemia), gastrointestinal issues, and skin reactions.
What Is the KCNJ11 Gene?
The KCNJ11 gene encodes the protein Kir6.2. The Kir6.2 is a potassium ion channel that regulates insulin release from the pancreas. So, Kir6.2 is essential for fine-tuning insulin release in response to changes in blood sugar levels, and in this way, helping to maintain proper glucose regulation in the body. So, any changes in the Kir6.2 protein can disrupt this process, and genetic mutations can cause these changes.
What Is the Link Between the KCNJ11 Gene and Gliclazide?
Finally, we came to the main question. Well, there are genetic mutations in the KCNJ11 gene, like rs5219. The rs5219 is a SNP (single nucleotide polymorphism), also known as E23K, located in the KCNJ11 gene. The two most common alleles are C and T for this SNP. Following the two most common alleles, every individual will have some of the following genotypes: CC, CT, or TT, where you inherit one from your biological mother and the other from your biological father.
Now, suppose you have a CC genotype, and you are taking gliclazide to treat diabetes mellitus. In that case, there is a high chance that you will have a decreased response to gliclazide compared to an individual with TT genotypes. Other clinical and genetic factors can influence the response to gliclazide in patients with diabetes mellitus, but this tells us that dosage adjustment is necessary for individuals with CC genotype.
This is just one of more than 1,500 similar cases that can be covered using your genotype data from 23andMe and AncestryDNA. I can generate a free-of-charge report if you want to check those out. You can check HERE the full list of gene drug interactions that can be checked for using 23andMe or AncestryDNA data.
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