NSAIDs – Impaired Metabolism (GS191 Genetic Marker)

By SWA

Summary
The GS191 genetic marker is associated with impaired metabolism of NSAIDs (non-steroidal anti-inflammatory drugs), potentially leading to increased toxicity or reduced clearance of these drugs. If this marker is present, NSAID use should be approached with caution or avoided, depending on the specific drug and the patient’s overall clinical context.

What is GS191?
The GS191 marker is a pharmacogenetic variant identified in certain genetic screening platforms, such as GeneSight and other pharmacogenomic tests. It is not a standard single nucleotide polymorphism (SNP) identifier like rs1057910 but is more likely a proprietary label used to summarize one or more relevant variants—particularly those that impact the metabolism of NSAIDs.

This marker typically reflects altered function in cytochrome P450 enzymes, especially:

  • CYP2C9, the primary enzyme responsible for metabolizing many NSAIDs including ibuprofen, diclofenac, and celecoxib.

  • CYP2C8 and CYP3A4, which also contribute to the metabolism of certain NSAIDs depending on the drug.

Individuals who carry the GS191 marker may have variants that classify them as intermediate or poor metabolizers of NSAIDs.

Metabolic Impact
When someone has the GS191 marker, their body may not process NSAIDs efficiently. This can result in:

  • Reduced or poor CYP2C9 metabolic activity

  • Slower clearance of NSAIDs from the bloodstream

  • Elevated plasma concentrations of the drug

This impaired metabolism increases the risk for a number of adverse effects:

  • Gastrointestinal toxicity, including ulcers and bleeding

  • Renal (kidney) toxicity, such as reduced glomerular filtration and acute kidney injury

  • Cardiovascular risks, including elevated blood pressure and risk of thrombotic events

Clinical Recommendations

Use NSAIDs with caution if GS191 is present:

  • Begin with the lowest effective dose

  • Use for the shortest duration necessary

  • Monitor the patient closely for signs of toxicity, particularly gastrointestinal, renal, or cardiovascular complications

Avoid certain NSAIDs when possible:

  • High-risk NSAIDs such as diclofenac, piroxicam, and indomethacin should generally be avoided in patients with impaired metabolism

  • If NSAIDs must be used, consider alternatives or selective agents with lower risk

Safer alternatives include:

  • Acetaminophen (paracetamol), provided there are no significant liver issues

  • COX-2 selective inhibitors (e.g., celecoxib), though still metabolized by CYP2C9 and requiring caution

  • Non-NSAID analgesics, depending on the condition being treated

Clinical consultation is recommended:
Pharmacists and genetic counselors can help interpret pharmacogenetic test results. They may recommend specific NSAID options or adjustments based on the individual’s genotype and clinical profile. Following genotype-guided therapy can significantly reduce the risk of adverse drug reactions.

Example Drugs Affected by GS191

 

Conclusion

The presence of the GS191 marker indicates a genetically reduced ability to metabolize NSAIDs, primarily through the CYP2C9 pathway. This can lead to elevated drug concentrations, longer duration in the body, and a higher likelihood of serious side effects. By identifying this marker through pharmacogenetic testing, healthcare providers can make more informed decisions, adjust dosages, or recommend safer alternatives for pain and inflammation management.

 

References

The dangers of NSAIDs: look both ways
Non-steroidal anti-inflammatory drugs (NSAIDs) are responsible for 30% of hospital admissions for ADRs, mainly due to bleeding, heart attack, stroke, and renal damage.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4809680/

Cardiovascular Risk with Non-steroidal Anti-inflammatory Drugs: Clinical Implications
https://pmc.ncbi.nlm.nih.gov/articles/PMC4206767/

Nonsteroidal Anti-inflammatory Drug (NSAID) Toxicity Workup
https://emedicine.medscape.com/article/816117-workup

 

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

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