What is heartburn, and how might DNA influence its treatment?

Heartburn, sometimes called acid reflux, is an all-too-common condition that leaves sufferers feeling nauseous and confused. It’s hard to know exactly what’s causing it, let alone what to do about it. Fortunately, in the late 1980s, scientists introduced omeprazole, the active ingredient in many heartburn medications, to US markets. In its nearly three decades of use, it’s become clear that some people respond to omeprazole differently: some feel its effects much longer than average, while others need higher doses to feel any effects at all.

So how do you know if drugs like omeprazole are likely to be more, or less, effective against heartburn in you? The answer may lay in Mayo Clinic’s GeneGuide.

GeneGuide is an educational tool that helps people learn about genetics and their health by exploring their own DNA. Part of that exploration includes a look at a gene in your DNA, CYP2C19, which helps your body metabolize omeprazole.

How omeprazole works

Heartburn is a condition where the acid in a person’s stomach, hydrochloric acid to be precise, splashes up into the esophagus—the tube running from your mouth to your stomach. When this acid hits the esophagus, it causes a burning sensation because the esophagus is not equipped to deal with its extreme properties. Hydrochloric acid destroys protein structures pretty well, and that’s a good thing: acid helps us break down foods and also helps keep our stomachs clear of bacteria. To protect our stomach cells from the acid, they’re coated in a special kind of mucus that blocks most of it, and neutralizes what it can’t block1,2.

 

The amount of acid that we produce has to be just right

The amount of acid that we produce has to be just right—too little and we may be at risk of stomach infections and other digestive problems; too much and you may experience heartburn or ulcers. When we produce too much acid, the obvious fix is to get our bodies to stop making so much of it. That’s where omeprazole comes in1,2.

Omeprazole is a molecule that essentially blocks the stomach’s ability to produce acid, but it can only do this in its complete form. Sometime after taking omeprazole, specialized proteins—known as enzymes—in a person’s liver will begin to break the drug down (or metabolize it). Once the liver metabolizes omeprazole, it no longer works. So omeprazole’s ability to help us with stomach acid problems is dependent on how quickly the liver breaks it down3.

How our DNA affects omeprazole

Our livers are able to break down omeprazole using an enzyme known as CYP2C19, a protein made by a gene of the same name. Researchers have found that some people inherit small differences in their CYP2C19 gene that affect how it works. For example, some people’s CYP2C19 gene makes a CYP2C19 protein that is extremely efficient—meaning it breaks down omeprazole much faster than it normally would. As a result, people with this version of the gene are likely to need much more omeprazole in order to get relief from some conditions like heartburn. These people are known as “ultra rapid metabolizers.”3

 

Some people are ultra-rapid metabolizers of omeprazole

On the other end of the spectrum are “poor metabolizers.” These people inherit a version of the CYP2C19 gene that prevents the protein from being made, or in some cases prevents it from working as well when it is made. As a result, poor metabolizers are likely to be slower when it comes to metabolizing omeprazole and will thus feel its effects longer than people normally would3.

It turns out that there are many other factors that can influence how quickly (or slowly) your body metabolizes omeprazole including your age, other medications you’re taking, and even your health3. Mayo Clinic GeneGuide analyzes your DNA to see which versions of the CYP2C19 gene you’ve inherited, and then discusses the many factors—both genetic and environmental—that can affect how a person responds to omeprazole treatment.

So, are you likely to be an ultra rapid metabolizer, a poor metabolizer, or something in between? The answer is just a few clicks away.

 

1“Symptoms & Causes of GER & GERD.” National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Health and Human Services, 1 Nov. 2014, www.niddk.nih.gov/health-information/digestive-diseases/acid-reflux-ger-gerd-adults/symptoms-causes.

2“Definition & Facts for GER & GERD.” National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Health and Human Services, 1 Nov. 2014, www.niddk.nih.gov/health-information/digestive-diseases/acid-reflux-ger-gerd-adults/definition-facts.

3Dean, Laura. “Omeprazole Therapy and CYP2C19 Genotype.” Medical Genetics Summaries [Internet]., U.S. National Library of Medicine, 8 Mar. 2016, www.ncbi.nlm.nih.gov/books/NBK100895/.

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