Alpha-1 antitrypsin deficiency (SERPINA1): what Pi*Z and Pi*S carriers should know

Genetics explainer · Updated June 2026

What alpha-1 antitrypsin does

Alpha-1 antitrypsin is a protein your liver makes and releases into the bloodstream. Its main job is to protect tissues — especially the delicate tissue of the lungs — from enzymes that the body releases during inflammation. Think of it as a shield: it keeps those enzymes from breaking down healthy tissue once they've done their job.

The protein is produced from instructions in the SERPINA1 gene. Certain variants in this gene change the protein so that less of it reaches the bloodstream, or so the version that's made works less effectively. The result is alpha-1 antitrypsin deficiency — less of the protective shield in circulation.

The SERPINA1 variants: PiZ and PiS

Most people inherit two normal copies of SERPINA1, written as the M type. The two variant alleles people typically check are:

• Pi*Z — the more significant of the two. The Z allele is the main variant associated with alpha-1 antitrypsin deficiency, and two copies are linked to the lowest protein levels.
• Pi*S — generally milder than Z on its own, and most relevant when it appears together with a Z allele.

You inherit one allele from each parent, so the combination matters. Broadly:

• MM — two normal copies; the common variants are not present.
• MZ or MS — a single variant copy. You're a carrier. Carriers usually have only a mild reduction in protein and most never develop problems.
• SZ — one S and one Z; an intermediate picture.
• ZZ — two Z copies, linked to the lowest levels and the genotype most associated with clinical deficiency. This is the combination most worth discussing with a clinician.

Why most carriers are mild

This is the part that matters most for a single-copy result. Carrying one PiZ or PiS allele — being MZ or MS — usually means a mild reduction in protein, and most carriers never develop symptoms. The genetics describe a predisposition, not a diagnosis.

Even among people with two variant copies, the picture varies a great deal from person to person. Age, smoking, other exposures, and individual differences all influence whether low protein levels ever translate into actual lung or liver problems. So a carrier result on a raw-data file is a reason to ask a question, not an answer in itself.

Why smoking matters enormously

If there's one thing to take away, it's this: with low alpha-1 antitrypsin, not smoking is the single most important protective step.

Here's the logic. Alpha-1 antitrypsin shields lung tissue from enzymes released during inflammation. Tobacco smoke does two unhelpful things at once — it ramps up the enzyme load in the lungs, and it reduces how well alpha-1 antitrypsin works. In someone with normal protein levels, the shield can keep up. In someone with low levels, the balance tips toward tissue damage, and over years that can accelerate the kind of lung damage seen in emphysema and COPD.

That's why the same genetics can play out so differently: a person with low protein levels who never smokes may stay well for life, while smoking can substantially raise the risk. Avoiding tobacco smoke — and secondhand smoke — is the clearest, most actionable step. It's worth raising any exposures with your doctor.

The liver side

SERPINA1 variants can also affect the liver, and the mechanism is different from the lungs. With the Z variant, some of the misshapen protein can build up inside liver cells rather than being released into the blood. In a minority of people this can contribute to liver issues over time. As with the lungs, most carriers are unaffected, and whether anything develops varies widely between individuals. This is simply a reason that any evaluation looks at both lung and liver health, and why a doctor — not a raw-data file — is the right place to sort it out.

How a deficiency is actually confirmed

Alpha-1 antitrypsin deficiency is confirmed in the clinic, not by reading DNA letters. A doctor can order a blood test that measures your actual alpha-1 antitrypsin level and, if needed, identifies the specific protein type. Those results — together with your symptoms, history, and any lung or liver findings — are what establish whether a real deficiency is present and what, if anything, to do about it.

Genetic results can support the picture and prompt the right conversation, but the blood tests are what matter. If your raw data shows a PiZ or PiS allele, the sensible next move is to mention it to your doctor and let proper testing fill in the rest.

Looking it up safely

Your genome is the one piece of data you can never change, so the safest way to read any health marker is on your own device rather than uploading your file to a server. For the full genotype-by-genotype breakdown, see SERPINA1 / alpha-1 antitrypsin in our gene library. To search your own file for these markers right in your browser with nothing uploaded, try our DNA explorer. And for more plain-language explainers like this one, browse the Quanome blog.

Frequently asked questions

What is alpha-1 antitrypsin deficiency?

It is an inherited condition in which the body makes too little working alpha-1 antitrypsin, a protein that protects the lungs. It is linked to the SERPINA1 gene, and the two variants people most often check are Pi*Z and Pi*S.

I'm a Pi*Z or Pi*S carrier. Should I be worried?

A single copy makes you a carrier, and most carriers have normal or near-normal protein levels and never develop symptoms. A carrier result is a reason to ask your doctor a question, not a diagnosis. The biggest single thing within your control is not smoking.

Why does smoking matter so much with SERPINA1 variants?

Alpha-1 antitrypsin shields lung tissue from enzymes released during inflammation. Smoking both increases that enzyme load and lowers the protein's effectiveness, so it accelerates lung damage far more in people with low levels than in others. Avoiding smoke is the most important protective step.

How is alpha-1 antitrypsin deficiency actually confirmed?

It is confirmed by a doctor with blood tests that measure your alpha-1 antitrypsin level and identify the protein type, not by reading raw DNA alone. Genetic results can support the picture, but the blood tests determine whether a real deficiency is present.