Everything we consume is made of molecules that our bodies can detect, use, or eliminate. When we drink water, for example, we rely on an arsenal of highly evolved tools that help us use it in specific ways and get rid of the water we don’t need. The same is true for the countless other molecules we consume, from sugars, to caffeine, to ingredients in medications.
One of the bigger tools in our arsenal is a group of proteins known as the cytochrome P450 (CYP) enzymes. Many of these enzymes are produced in the liver where they help process or break down chemicals in the body. A particularly well-known CYP enzyme is called CYP2C9. Among its many roles, CYP2C9 is responsible for metabolizing ibuprofen1. Researchers have found that many people inherit a variant—a change in the DNA sequence—that alters the CYP2C9 enzyme’s ability to metabolize ibuprofen. This means that depending on a person’s DNA sequence, they may be able to metabolize ibuprofen faster, or slower, than others. This link between genetics and drug response is studied in the field of pharmacogenomics.
Researchers have found that some people metabolize ibuprofen slower than others
Pharmacogenomics is an important and growing field because it helps explain why some people have significantly different responses to medicine compared to others. A good example of this is the pharmacogenomics association between the CYP2C9 gene and ibuprofen metabolism.
Ibuprofen is an over the counter pain reliever used around the world, and there’s a good chance you have a bottle of it in your own medicine cabinet. Researchers have found that some people metabolize ibuprofen slower than others, which leads to a buildup of ibuprofen in the bloodstream. Chronically high levels of drugs like ibuprofen in the blood have been shown to increase the odds of stomach ulcer development and gastric bleeding2.
Studies show that people who experience stomach ulcers when taking ibuprofen are more likely to have a variant in their CYP2C9 gene than people who don’t have an ulcer. Put another way, variants in the CYP2C9 gene may lead to increased ibuprofen levels in the blood, and increased odds of developing a stomach ulcer3,4.
Large scale studies have also found that variants in the CYP2C9 gene are fairly common in some populations—one variant associated with a change in ibuprofen metabolism is present in as many as 14 percent of people with Caucasian ancestry4. Research has shown the association between CYP2C9 variants and altered ibuprofen metabolism in populations of various different ancestries, but, more research is needed to better understand how other genetic variants associated with ethnicity may alter the impact of CYP2C9 variants3,4.
Whether it’s ibuprofen or another medication, the way our body responds to chemicals is dependent on a number of factors, including genetics. Mayo Clinic GeneGuide™ includes analysis of variants in the CYP2C9 gene, which can help you learn about your own body’s ibuprofen response—in addition to a variety of other health-related DNA insights and educational resources.
1Thorn, Caroline F. et al. “PharmGKB Summary: Caffeine Pathway.” Pharmacogenetics and Genomics 22.5 (2012): 389–395. PMC. Web. 24 Aug. 2018.
2Wallace, John L. “How Do NSAIDs Cause Ulcer Disease?” Best Practice & Research Clinical Gastroenterology, vol. 14, no. 1, 2000, pp. 147–159., doi:10.1053/bega.1999.0065.
3Daly, Ann K. et al. “Pharmacogenomics of CYP2C9: Functional and Clinical Considerations†.” Journal of Personalized Medicine 8.1 (2018): 1. PMC. Web. 24 Aug. 2018.
4Figueiras, Adolfo et al. “CYP2C9 Variants as a Risk Modifier of NSAID-Related Gastrointestinal Bleeding: A Case–control Study.” Pharmacogenetics and Genomics 26.2 (2016): 66–73. PMC. Web. 24 Aug. 2018.