APOA5 Genotype (p.Ser19Trp)

Triglycerides are the main form of fat carried in your blood, and how well your body clears them depends partly on the genes you inherit. This test looks at one of those genes, APOA5, and at a common change in it called S19W (rs3135506). The change swaps a single DNA letter, and in study after study it has been linked to higher triglyceride levels.

It is a common change, not a rare disease mutation. Carrying it tilts the odds toward higher triglycerides, but your level also depends on your weight, diet, alcohol intake, other health conditions, and variants in more than 30 other genes. That is why this result never replaces a triglyceride blood test.

What This Variant Actually Does

The APOA5 gene makes apolipoprotein A-V (apoA-V), a protein that plays an important role in setting triglyceride levels. It is thought to help break down the triglycerides carried in VLDL and chylomicrons, the particles that move fat from your liver and gut through your bloodstream. In mice, more apoA-V means lower triglycerides.

S19W changes the 19th building block of the protein from serine (S) to tryptophan (W). That position sits in the signal peptide, a short leading section that works like a shipping label, guiding the protein out of the cell. In lab experiments published in 2005, the tryptophan version of this label cut the amount of a test protein released from liver-derived cells by about half. A later study, however, found that people carrying the variant had higher, not lower, apoA-V levels in their blood, so exactly how the change raises triglycerides is still not settled. The link with triglycerides itself has held up across many populations.

How Much It Raises Triglycerides

Researchers tied this variant to triglycerides in 2002. In one study, it was more than three times as common in people with triglycerides in the top 10 percent as in people in the bottom 10 percent. In another, carriers had higher triglycerides whether they ate their usual diet, a high-carbohydrate diet, or a high-fat diet. In a third group of 2,660 people, it was linked to higher triglycerides in men and women of white, African American, and Hispanic background alike.

The size of the effect depends on how many copies you carry. In one study of 2,808 healthy middle-aged men, the small number with two copies had triglycerides about 52 percent higher on average than men with none; with so few men, that figure is only a rough estimate. Each copy adds to the effect, so one copy has a smaller one. In UK Biobank, a study of 363,228 people, each copy was linked to higher triglycerides and, to a lesser degree, higher apolipoprotein B and LDL cholesterol and lower HDL cholesterol.

Even so, researchers who specialize in triglyceride genetics describe S19W as a risk allele, not a cause. A 2024 review explains that it raises the odds of high triglycerides when the rest of your metabolism allows, and that it is one of many common variants counted in polygenic risk scores for high triglycerides.

Heart Disease Risk

Triglycerides travel in particles that also carry cholesterol, and these particles and their leftovers (remnants) can lodge in artery walls. A 2021 European Atherosclerosis Society consensus concluded that genetic, population, and clinical trial evidence strongly supports a causal link between these particles and heart attack, ischaemic stroke, and narrowing of the aortic valve.

APOA5 genetics is part of that evidence. In a Danish study of 5,705 people who had a heart attack and 54,408 who had not, the highest-risk combinations of S19W and two other APOA5 variants raised nonfasting triglycerides by up to 68 percent and came with 87 percent higher odds of a heart attack (odds ratio 1.87).

For S19W on its own, the picture is unclear. A 2020 pooled analysis of mostly small case-control studies reported higher odds of coronary artery disease in people with two copies, but found no clear increase with one copy. Its results varied from study to study, some of the data it pooled contain evident errors, and its result rests on few people with two copies, so its estimate is not reliable. An earlier pooled analysis, from 2013, which compared individual gene copies rather than people with two copies, found no clear link. In the EPIC-Norfolk study, which followed people over time, the variant was no more common in the 1,034 people who developed coronary artery disease than in 2,031 who did not, even though carriers had higher triglycerides.

What this means for you: any effect of this variant on your heart appears to run mainly through triglyceride-rich particles, which show up in your triglycerides and apolipoprotein B, both of which you can measure and change. Your measured triglycerides, LDL cholesterol, blood pressure, blood sugar, and smoking status tell you far more about your heart risk than this genotype does.

How Common It Is

S19W is common. In the gnomAD v4.1 reference database, about 6.2 percent of APOA5 gene copies carry it, and roughly 1 in 9 people carry one copy. It is similarly common in people of European and African or African American ancestry (about 6.3 percent of gene copies in each), more common in people with Latin American ancestry (about 14 percent), and very rare in people of East Asian ancestry (under 0.1 percent). Two copies (C/C) is uncommon, about 1 in 230 people in gnomAD.

How Results Are Reported

Your report shows the two DNA letters at this position, one inherited from each parent, printed on the forward strand of chromosome 11 (G or C). G is the usual letter, which codes for serine; C is the variant, which codes for tryptophan. Scientific papers usually describe the same change as C>G (c.56C>G) or S19W, because the APOA5 gene is read from the opposite strand. They are the same variant. A one-copy result can be printed as G/C or C/G; the order of the letters makes no difference.

ClinVar, the US public database of variant classifications, gives it an overall classification of benign or likely benign, meaning it does not cause a genetic disease on its own, and also records it as a risk factor for hypertriglyceridemia. Your genetics report may call it a risk factor too. Both descriptions fit: it raises the odds of high triglycerides without causing disease by itself.

What this means for you: none of these three results tells you your triglyceride level. Treat the genotype as context and the blood test as the answer.

The Blood Test Still Decides

A standard lipid panel measures your triglycerides. The European Atherosclerosis Society treats a fasting level below 100 mg/dL as optimal, says cardiovascular risk becomes clinically relevant above 150 mg/dL, and links levels above 880 mg/dL to a high risk of pancreatitis, a serious inflammation of the pancreas. The Endocrine Society classifies 150 to 999 mg/dL as mild to moderate hypertriglyceridemia and levels above 1,000 mg/dL as severe. A genotype at one position cannot place you in one of those ranges; only the measurement can.

This variant is best read as context. If your triglycerides run high and you carry it, it may be one small contributor among many, alongside weight, diet, alcohol, other health conditions and other genes; the test cannot say how much of your level it explains. If they run high and you do not carry it, this particular variant is not part of the picture. A European Atherosclerosis Society panel on the genetics of high triglycerides concluded that routine genetic testing is not warranted to diagnose it, except in children and teenagers with severe high triglycerides; the blood test is what guides care.

Why You Only Need This Test Once

Your DNA does not change. Your rs3135506 genotype at 25 will be the same at 65, so there is no reason to repeat this test. Your triglycerides are a different story: they move with your weight, diet, alcohol intake, and blood sugar control, so your clinician may recheck them over time, especially after you make changes or start a treatment.

What to Do With Your Result

Whatever your genotype, the next steps are the same, and they center on the blood test:

• Measure your actual triglycerides: if you have not had a lipid panel recently, get one. It is the number guidelines use to decide whether anything needs to change.
• Start with the levers you control: for mild to moderately high triglycerides, guidelines recommend diet changes and weight loss first. That means cutting back on highly refined carbohydrates, eating seafood such as fatty fish, adding fiber-rich fruits, vegetables, and whole grains, avoiding excess alcohol, and choosing plant oils and nuts over animal fats.
• Very high levels are different: if your triglycerides are above about 880 to 1,000 mg/dL, see your clinician promptly. Treatment then starts right away, usually a medicine such as a fibrate together with a strict low-fat diet and cutting sugars and refined carbohydrates. Severe belly pain when your triglycerides are very high can be pancreatitis and needs urgent care.
• Look for other causes: guidelines recommend checking anyone with high triglycerides for secondary causes, other conditions that push triglycerides up. Excess weight, insulin resistance, and diabetes are common contributors.
• Know when medication comes in: treatment decisions rest on your measured triglycerides and overall cardiovascular risk, not on this genotype. European guidelines consider drug treatment for people at high cardiovascular risk whose triglycerides stay above 200 mg/dL after other causes are addressed. For heart protection, a European Atherosclerosis Society panel points to statins, which lower LDL cholesterol and reduce heart disease risk whatever your triglyceride level.
• Point family members to the blood test: high triglycerides cluster in families, and experts recommend that relatives have their triglycerides checked rather than routine genetic testing.

Carrying this variant is a nudge toward higher triglycerides, not a verdict. The blood test tells you where you actually stand, and the steps above are what move the number.