A GWAS in the Framingham cohort found that genetic variation at the IL1RL1 gene, functionally validated in cell culture, drives much of the variation in sST2 — a soluble protein linked to cardiovascular disease risk.
ST2 is a receptor protein produced in two forms: a membrane-bound version (ST2L) that triggers an immune response when it binds the signaling protein IL-33, and a soluble version (sST2) that circulates in blood and is thought to act as a decoy, soaking up IL-33 before it can trigger that response. Elevated sST2 in serum is associated with higher cardiovascular disease risk, which is why it is studied as a potential biomarker.
Ho et al. 2013 studied sST2 levels in 2,991 Framingham Offspring Cohort participants and found that while clinical and environmental factors explained some of the variation, much of it was genetically driven. A GWAS found multiple variants within IL1RL1 — the gene that encodes ST2 itself — associated with sST2 concentration. Five missense variants raising sST2 levels mapped to the receptor's intracellular domain, a part of the protein absent from the soluble form; in a cell culture model, these same variants were shown to increase sST2 by inducing IL-33 expression and enhancing the cell's response to it, directly confirming the genetic association with a functional mechanism rather than leaving it as a statistical correlation alone.
This page's 4 IL1RL1 variants come directly from the paper's own headline finding. The other 4 — in or near IL1R1, IL1RL2, SLC9A4, and IL18RAP — sit in the same interleukin-1-receptor gene cluster on chromosome 2 as IL1RL1 itself, consistent with the same broader regional signal rather than four independent discoveries.
sST2 is measured directly with a blood test, not estimated from genotype, and no variant on this page is used clinically to interpret an sST2 result or assess cardiovascular risk. sST2 is studied as a research and emerging clinical biomarker — these variants describe genetic contributors to its baseline level, not a risk prediction tool on their own.
Where sST2 is used clinically (for example, alongside other markers in heart failure risk assessment), interpretation is guided by the measured blood level and established clinical thresholds — not by genotype.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Serum sST2 Levels comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 8 of 8 linked studies with a resolved discovery ancestry.
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Serum sST2 Levels. MyGeneLog™. https://www.mygenelog.com/conditions/sst2-levels
sST2 is the soluble form of the ST2 receptor protein, thought to act as a decoy for the signaling protein IL-33. Elevated sST2 in blood is associated with higher cardiovascular disease risk.
In 2,991 people, it found that variants in IL1RL1 (the gene encoding ST2) drive much of the genetic variation in sST2 levels, and confirmed this in cell culture experiments showing the variants directly increase sST2 production.
No. sST2 is measured directly with a blood test, and clinical risk assessment uses the measured level and established thresholds, not genotype.
IL1RL1 and its neighboring genes (IL1R1, IL1RL2, IL18RAP) sit together in an interleukin-1-receptor gene cluster on chromosome 2, so a single genetic signal in that region can produce associations across several nearby genes at once.
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