Pharmacogenomics 101: How Your DNA Affects Drug Response

Have you ever wondered why a medication that works perfectly for a friend gives you terrible side effects? Or why a drug that's supposed to help does nothing for you? The answer is often in your DNA.

Pharmacogenomics (PGx) studies how genetic variations affect drug metabolism, efficacy, and side effects. Your genes encode the enzymes that process medications — and variations in these genes can make you metabolize drugs faster or slower than average.

The cytochrome P450 (CYP) enzyme family is responsible for metabolizing approximately 75% of all prescription medications. The most clinically important enzymes are:

CYP2D6 — Metabolizes ~25% of drugs including codeine, tramadol, tamoxifen, many antidepressants (fluoxetine, paroxetine), and beta-blockers (metoprolol). About 6-10% of Caucasians are poor metabolizers.

CYP2C19 — Metabolizes clopidogrel (Plavix), PPIs (omeprazole), some antidepressants (escitalopram, sertraline), and voriconazole. About 2-5% of Caucasians and 15-20% of East Asians are poor metabolizers.

CYP2C9 — Metabolizes warfarin, phenytoin, and NSAIDs. Variants can dramatically affect warfarin dosing (2-3x dose differences).

CYP3A4/5 — The most abundant liver CYP enzyme. Metabolizes ~50% of drugs including statins, immunosuppressants, and many cancer drugs.

Based on your CYP gene variants, you're classified into metabolizer categories:

🔴 Ultra-Rapid Metabolizer (UM): You break down the drug extremely fast. Standard doses may be ineffective because the drug clears too quickly. For prodrugs (like codeine → morphine), this can be dangerous because you convert too much active metabolite.

🟡 Rapid/Normal Metabolizer (RM/NM): Standard dosing is appropriate. This is the 'reference' category that standard drug doses are designed for.

🟠 Intermediate Metabolizer (IM): You metabolize drugs somewhat slower than normal. May need dose adjustments for some medications.

🔴 Poor Metabolizer (PM): You metabolize the drug very slowly. The drug accumulates to higher levels, increasing side effects and toxicity risk. For prodrugs, the drug may be ineffective because you can't convert it to the active form.

Pharmacogenomics isn't theoretical — it saves lives and reduces suffering:

Clopidogrel + CYP2C19: After stent placement, CYP2C19 poor metabolizers on clopidogrel have a 3.6x higher risk of cardiovascular events because they can't activate the drug. CPIC guidelines recommend alternative antiplatelet therapy (prasugrel or ticagrelor).

Codeine + CYP2D6: In 2013, the FDA added a black box warning after CYP2D6 ultra-rapid metabolizer children died from morphine toxicity after receiving standard codeine doses post-tonsillectomy.

Warfarin + CYP2C9 + VKORC1: Genetic dosing algorithms can predict up to 50% of warfarin dose variability, reducing bleeding events and time to therapeutic range.

Abacavir + HLA-B*5701: HLA-B*5701 screening before abacavir (HIV drug) eliminated severe hypersensitivity reactions, going from ~8% incidence to essentially 0%.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes peer-reviewed, evidence-based guidelines for gene-drug pairs. As of 2025, CPIC has published guidelines for over 25 gene-drug pairs with actionable recommendations.

CPIC guidelines are graded by evidence level: • Level A: Strong evidence, prescribing action recommended • Level B: Moderate evidence, prescribing action recommended • Level C: Limited evidence, optional action

GenomeInsight's pharmacogenomics analysis follows CPIC guidelines where applicable. Every recommendation cites the relevant CPIC guideline and evidence level.

1. Don't panic or change medications on your own. Pharmacogenomic results are one factor among many that your doctor considers.

2. Share results with your prescriber. Print or share your GenomeInsight pharma report with your doctor and pharmacist. Many pharmacists now specialize in pharmacogenomics.

3. Ask about alternatives. If you're a poor metabolizer for a medication you're taking, ask your doctor if there are alternatives metabolized by different enzymes.

4. Consider the Medication Scanner. GenomeInsight's medication scanner cross-references your current medications against all your pharmacogenomic results simultaneously.

5. Keep results accessible. Your pharmacogenomic genotype doesn't change. These results are useful for every future medication decision.