Pharmacogenomics testing at home: Testing Process and Background

Pharmacogenomics looks at how your genes shape the way your body handles medications. Below you will find how at-home testing works, then a deeper look at the science: star alleles, CYP450 enzymes, what a poor metabolizer result means and how guidelines turn genetic data into safer prescribing.

Undergoing Pharmacogenomics testing may only require you to order a PGx testing kit, do a buccal swab, and return the sample in the prepaid envelope you have received along with your kit. Receive your reports online and use this data to get the best treatment possible. Complete details on how the PGx tests at home work.

Overview of Pharmacogenomics:

Pharmacogenomics, a branch of pharmacology, is the study of how a person’s genome (complete set of genes) can influence their response to certain medications. This is often abbreviated as PGx.

How does it work?

Different enzymes are responsible for metabolizing different drugs. Based on your DNA, PGx tests give insights into how certain enzymes in your body respond to different medications. There are 4 main types of metabolizers: poor, intermediate, normal (sometimes called extensive), and ultrarapid metabolizers.

As per NIH, “the most commonly used enzymes for medical purposes are monoamine oxidase and cytochrome P450.”

Can medicines affect individuals differently?

Drugs can affect individuals differently and there are certain factors behind this, such as the age of the individual or drug-drug reactions. The FDA includes pharmacogenomic information in the labels of numerous drugs, including many used in mental health treatment, because they may affect individuals differently. Adverse drug reactions are classified into 6 types and most are connected to dosages. People may also have critical reactions to certain medications, thus doctors usually take your previous medication history and if you have allergies to any specific salt.

Poor metabolizers:

If you are a poor metabolizer of a specific drug, your body will experience difficulty metabolizing it and removing it from your system. Standard drug doses consumed by a poor metabolizer causes increased drug concentration in the bloodstream, which can raise the risk of side effects and toxicity. Prodrugs work the other way around: codeine (CYP2D6) and clopidogrel (CYP2C19) must be activated by the enzyme, so poor metabolizers make less of the active drug and may get little benefit.

Intermediate Metabolizers

Intermediate metabolizers have reduced enzyme activity, somewhere between poor and normal metabolizers. Many drugs work as expected at standard doses, but for some medications your prescriber may adjust the dose or choose an alternative. For prodrugs such as clopidogrel, reduced activity can mean less of the active drug and a weaker effect.

Normal (Extensive) Metabolizers

Extensive metabolizers, also known as normal metabolizers have normal or average drug metabolism rates, meaning their bodies clear most drugs efficiently. Standard drug doses are processed and eliminated normally, thus typically they do not experience issues consuming standard doses.

Ultrarapid metabolizers

Ultrarapid metabolizers have a very high rate of metabolism, often because they carry extra copies of a gene or variants that increase enzyme activity. While they clear drugs rapidly, this can lead to suboptimal drug effectiveness. The drug may be eliminated too quickly before it can exert its therapeutic effects, so a different dose or a different drug may be needed.

For prodrugs the risk is reversed: ultrarapid CYP2D6 metabolizers turn codeine into morphine too quickly and can have serious side effects. In some cases, this fast clearance can lead to increased variability in drug response and treatment challenges, necessitating adjustments in dosing.

It’s important to note that while you may be a normal or ultrarapid metabolizer in the case of one enzyme, you can perhaps be a poor metabolizer of another enzyme. Moreover, it is worth noting that while Genetic Testing for Mental Health holds special importance, this is not the only area being privileged by this testing. Pharmacogenomic testing is helping doctors in numerous therapeutic areas.

Pharmacogenomics testing at home from RPh Labs provides insights into your genetic makeup and your body’s response to 240+ medications.

Pharmacogenomics vs pharmacogenetics: is there a difference?

You will often see both words used for the same thing, and in everyday conversation they are interchangeable. Strictly speaking, pharmacogenetics usually refers to how a single gene affects the response to a drug. Pharmacogenomics takes a wider view and looks at many genes at once.

Both are shortened to PGx. The NHGRI genetics glossary describes it as the study of how genes affect a person’s response to drugs. Modern tests reflect the broader approach: instead of checking one gene before one drug, a panel checks many genes that are linked to hundreds of medications.

The practical takeaway is simple. Whether your report says pharmacogenetic or pharmacogenomic, it is describing the same kind of information: which versions of drug-related genes you carry and what that may mean for your prescriptions. For a plain-language overview, see what PGx testing is.

How star alleles and diplotypes describe your genes

Labs do not report every letter of your DNA. They report named versions of each gene, called star alleles. Each star allele is a specific combination of variants with a number, such as CYP2C19*1, *2 or *17. The official catalog for many drug genes is kept by PharmVar.

Because you inherit one copy of each gene from each parent, your result is a pair, written like CYP2C19 *1/*2. This pair is called a diplotype. Some star alleles work normally, some have reduced function, some have no function and a few have increased function.

The lab combines the two versions to predict how active the enzyme or protein will be. For CYP2D6, labs also check for whole-gene deletions and extra copies, since some people carry more than two working copies. That is one reason CYP2D6 results can be more complex than other genes.

These gene versions also explain why your result does not change. They are part of your inherited DNA, so a PGx result stays valid for life, even though the recommendations attached to it can be updated.

The CYP450 enzymes behind most drug metabolism

Drug metabolism is the process of changing a medication into forms the body can use or remove. Much of it happens in the liver, and the cytochrome P450 family does a large share of the work. The CYP450 enzymes most often included in PGx testing are:

• CYP2D6: many antidepressants, antipsychotics and beta blockers, and the activation of codeine and tramadol.
• CYP2C19: clopidogrel activation, several SSRIs and most proton pump inhibitors.
• CYP2C9: warfarin, phenytoin and some anti-inflammatory drugs.
• CYP3A4 and CYP3A5: tacrolimus and a wide range of other drugs.
• CYP2B6: efavirenz and methadone, among others.

CYP450 enzymes are only one part of drug metabolism. Other enzymes attach chemical groups to drugs so they can be removed. These include UGT1A1 (irinotecan and the processing of bilirubin), NAT2 (isoniazid and hydralazine) and TPMT and NUDT15 (thiopurines such as azathioprine and mercaptopurine). A good panel covers both groups.

What a poor metabolizer result really means

A poor metabolizer has little or no activity of a specific enzyme. What that means for you depends on whether a drug is active when you take it, or whether it needs the enzyme to become active.

When the drug is already active

If the enzyme clears an active drug, someone with little enzyme activity may have higher blood levels at standard doses. That can raise the risk of side effects. For example, CPIC guidance suggests lower starting doses or alternative drugs for some antidepressants in CYP2D6 or CYP2C19 poor metabolizers.

When the drug is a prodrug

Some medications, called prodrugs, must be converted before they work. Codeine and tramadol need CYP2D6, and clopidogrel needs CYP2C19. If you have very low activity of the needed enzyme, you may make too little of the active form and get less benefit, not more.

This kind of result applies to one gene only. You can have very low CYP2D6 activity and normal CYP2C19 activity. Your prescriber reads each gene against each medication, and any change to your treatment should be made with them.

Beyond enzymes: transporters, targets and immune genes

PGx is not only about how fast a drug is broken down. Some genes control how drugs move into cells, what the drug acts on or how the immune system reacts to it.

• Transporters: SLCO1B1 moves statins into the liver. Decreased function raises the risk of muscle problems with simvastatin. Read more in our guide to SLCO1B1 decreased function.
• Drug targets: VKORC1 is the target of warfarin. Along with CYP2C9, it helps predict how much warfarin a person needs.
• Immune genes: HLA-B*15:02 is linked to severe skin reactions to carbamazepine, and HLA-B*57:01 to abacavir hypersensitivity.
• Other genes: G6PD deficiency can cause red blood cell damage with certain drugs, and MT-RNR1 variants raise the risk of hearing loss with aminoglycoside antibiotics.

These genes do not fit the fast or slow metabolizer labels, so reports describe them with terms such as decreased function, positive or deficient.

Why genes are not the whole story in drug metabolism

Your genes set the starting point, but many other things affect drug metabolism day to day. A good prescriber considers all of them together.

• Other medications: strong CYP2D6 inhibitors such as fluoxetine, paroxetine and bupropion can make a normal metabolizer act as if the enzyme barely works. This is called phenoconversion.
• Foods and habits: grapefruit juice can block CYP3A4, and smoking speeds up CYP1A2.
• Age and organ function: older age and reduced liver or kidney function can slow how drugs are cleared.
• Adherence and dose: how and when a medication is taken also shapes the result.

This is why genetic results work best as one input, not the final word. Our article on CYP2D6 inhibitors goes deeper into drug interactions and phenoconversion.

Who turns pharmacogenomics research into guidance?

Knowing that a gene variant exists is only useful if there is agreement on what to do about it. Several public groups do that work.

• CPIC publishes peer-reviewed gene and drug guidelines that explain how to adjust therapy for a given result. Learn more on our CPIC page.
• The FDA includes pharmacogenomic information in many drug labels, from boxed warnings to dosing notes.
• PharmGKB gathers the research behind each gene and drug pair.
• PharmVar names and defines the star alleles labs report.

Guidance changes as research grows. RPh Labs updates reports when guidelines change, so the value of your one-time test can grow over time.

Common myths about PGx results

Genetic testing for medications is still new to many people, so a few misunderstandings come up often. Clearing them up makes it easier to use your report well.

• Myth: a result tells you which drug to take. A report shows how your genes may affect certain drugs. Your prescriber still chooses the medication based on your diagnosis, history and other factors.
• Myth: a normal result is useless. Normal findings are useful too. They tell your prescriber that standard dosing is a reasonable starting point for drugs linked to that gene.
• Myth: you need to repeat the test every year. Your inherited DNA does not change. What changes is the guidance, which is why updated reports matter more than new samples.
• Myth: results reveal your risk of disease. PGx panels focus on medication response. They are not designed to diagnose illness.
• Myth: if a drug is flagged, you must stop it. Never stop or change a medication on your own. A flag is a prompt to talk with your prescriber, who may adjust the dose, add monitoring or keep things as they are.

If a result surprises or worries you, write down your questions and bring them to your next appointment or pharmacist consultation. Our FAQ page also covers many common questions about testing and reports.

Putting pharmacogenomics to work in your own care

If you take, or expect to take, medications with known gene links, a PGx test can give your prescriber useful information before the next prescription is written. You can check your medications on our medication list by gene.

The RPh Labs at-home kit uses a cheek swab and covers 20 genes reported against more than 240 medications. Results are ready 7 to 10 business days after the sample reaches our lab, and every report is reviewed by a PharmD pharmacist, with a free consultation included.

Share your report with your prescriber and pharmacist, and never stop or change a medication on your own based on the results alone.

In Summary:

Adverse drug reactions are critical and can even cause death. PGx tests or pharmacogenomics testing is gaining popularity due to its clear insights into your genetic makeup, based on which you and your doctor can not only check which drugs to avoid but also set the right dosages based on your genome. These PGx tests do not have any strict expiration date, however, if you have been on critical medications it’s best to consult your healthcare for retesting.

Disclaimer: Please note that this blog is for informational purposes. Please consult a doctor before taking any medical action.

References:

https://pubmed.ncbi.nlm.nih.gov/1471165/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3299179/
https://www.ncbi.nlm.nih.gov/books/NBK442023/

Pharmacogenomics FAQ

Is pharmacogenomics testing at home easy?

Indeed. Simply order your kit online, do a cheek swab, and send back your sample in the RPh Labs prepaid envelope. Receive your test reports securely online.

What is pharmacogenomics?

Pharmacogenomics, a branch of pharmacology, is the study of how a person’s genome (complete set of genes) can influence their response to certain medications. This is often abbreviated as PGx.

What does PGx test tell?

A PGx test gives insights into your genetic makeup, showing how your body may respond to different medications. This helps in getting the right drugs with the right dosages.

Can I do a PGx test at home?

Yes, PGx testing is possible from the comfort of your home. It only requires a buccal swab. Check out how it works.

Do PGx test reports expire?

Although these reports do not have any specific expiration date. In case the report is too old and you have been on any critical medication, it is advisable to consult your doctor to determine if a new report would be beneficial.

Can I be a poor metabolizer for one drug and fine with another?

Yes. A poor metabolizer result applies to one enzyme. Drugs that rely on a different enzyme may be processed normally. For example, you could be a CYP2D6 poor metabolizer and a normal CYP2C19 metabolizer. Your prescriber looks at each medication and the gene that matters for it.

Why do star alleles have numbers like *1 and *2?

Star alleles are a naming system for versions of a gene. Each number stands for a defined set of DNA variants. *1 is usually the reference version with normal function, while other numbers can mean reduced, absent or increased function. PharmVar maintains the official definitions for many drug-related genes.

Do CYP450 enzymes change as I get older?

Your CYP450 genes do not change, but how well the enzymes work in practice can. Age, liver health, other medications and habits such as smoking can shift enzyme activity. This is why your prescriber combines your genetic results with your current health and medication list.

Does drug metabolism depend on ancestry?

The frequency of some star alleles differs between populations. That is why a person’s own genetic result is more useful than assumptions based on ancestry. A PGx test reads your actual genes, so decisions can be based on you rather than on group averages.

Is pharmacogenomics used in hospitals?

Yes. Many hospitals and health systems use PGx results for decisions such as clopidogrel after a heart stent or thiopurine dosing. Guidance from CPIC and FDA labeling supports this use. Results from a CLIA-certified lab can be shared with any clinician who treats you.