ACE inhibitors are among the most prescribed drugs for blood pressure and heart failure, and their best-known side effect — a dry, persistent cough — is the usual reason someone gets switched to a different drug. This page holds three variants from the one study that has looked at who makes that switch.
Angiotensin-converting enzyme (ACE) inhibitors are one of the most widely prescribed drug classes for high blood pressure, heart failure and kidney protection in diabetes. They work by blocking the enzyme that produces angiotensin II, a hormone that narrows blood vessels — and that same enzyme also breaks down bradykinin, a different signalling molecule. When ACE is blocked, bradykinin builds up, and in a meaningful minority of people that produces a dry, persistent, tickling cough that does not respond to cough medicine and resolves only when the drug is stopped.
That cough is the most common reason a doctor switches someone from an ACE inhibitor to an angiotensin receptor blocker (ARB) — a related drug that blocks angiotensin II's effect without touching bradykinin, and rarely causes the same cough.
The single study behind this page took a pragmatic approach to defining intolerance: rather than scoring cough severity directly, it compared 972 people who switched from an ACE inhibitor to an ARB against 4,189 who started an ACE inhibitor and stayed on it for at least two years, drawn from two cohorts — the Rotterdam Study in the Netherlands and GoDARTS in Tayside, Scotland. That is a real-world definition of intolerance: whatever combination of symptoms actually led to a change in prescription, not a single standardised measurement. The page rests on that definition rather than implying more precision than the study has.
Eight SNPs across four genes reached genome-wide significance. The strongest, rs2061538 in RBFOX3 — an RNA-binding protein gene — carried an odds ratio of 1.52. The other two variants on this page sit in MBOAT1 and GABRG2, from the same analysis. None of the four genes has an established, direct role in the cough mechanism described above; the study's own framing is that these results indicate a genetic contribution to ACE-inhibitor intolerance exists, not that it has explained how.
This page is about who ends up switched off an ACE inhibitor, in one study's data — not about the drug's effectiveness, not about a specific measured symptom, and not a CPIC dosing pair with prescribing guidance attached. There is no genotype-guided prescribing recommendation for ACE inhibitors, and nothing here changes how the drug is started or dosed.
The symptom that actually matters. A new, dry, persistent cough after starting an ACE inhibitor is common, usually harmless, and usually resolves within days of stopping the drug — but it is worth reporting to whoever prescribed it, both to confirm the cause and because ARBs are a straightforward alternative. A much rarer but serious reaction, angioedema — swelling of the face, lips, tongue or throat — needs emergency care. Nothing on this page distinguishes the two, and neither should wait on a genotype.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about ACE Inhibitor Intolerance comes down to these specific, well-studied positions — not a diagnosis.
MBOAT1 · rs10946364
See detailed info →GABRG2 · rs77370934
See detailed info →Databases, guidelines and references
Not with any precision. This page describes one study's genetic findings on who ends up switched to a different drug, not a mechanism for the cough itself. The useful step is telling whoever prescribed the ACE inhibitor about the cough; switching to an angiotensin receptor blocker usually resolves it.
No. The odds ratios here are modest and come from one study in two European cohorts. Nothing on this page is used to decide who starts an ACE inhibitor or at what dose.
No, and the distinction matters. The dry cough is common, not dangerous, and resolves after stopping the drug. Angioedema — swelling of the face, lips, tongue or throat — is much rarer and is a medical emergency. This page does not distinguish between them, and a swelling reaction needs emergency care regardless of genotype.
Because the study defined intolerance pragmatically — who actually got switched to a different drug — rather than measuring the cough directly, and a genome-wide scan has no way to be steered toward a mechanism it already expects. The study's own conclusion is that a genetic contribution exists, not that these genes explain how it works.
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