ACE Gene Test (Angiotensin-Converting Enzyme)

Testing the ACE gene can help you:

• Identify your II, ID, or DD genotype, which determines baseline ACE enzyme activity and influences cardiovascular and performance characteristics.
• Understand endurance vs power predisposition, with the I allele associated with endurance capacity and the D allele linked to power/strength.
• Clarify cardiovascular risk context, including hypertension, left ventricular hypertrophy, kidney disease progression, and fibrinolytic function influenced by ACE-regulated PAI-1.
• Inform personalised training tailored to genetic strengths, recovery capacity, and cardiovascular response to training modalities.
• Support altitude planning, as the I allele is associated with better high-altitude performance and mountaineering success.
• Add genetic context for ACE inhibitor medication response (clinical utility remains uncertain).

Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that converts angiotensin I into angiotensin II, a potent vasoconstrictor that raises blood pressure by binding to vascular AT1 receptors. ACE also inactivates bradykinin, a vasodilator that lowers blood pressure.

The ACE gene provides instructions to produce this enzyme, and a common insertion/deletion polymorphism (I/D) in intron 16 influences circulating and tissue ACE activity.

The I/D polymorphism involves the presence (insertion, I allele) or absence (deletion, D allele) of a 287 base-pair DNA fragment. Genotypes create three activity phenotypes: II (lowest ACE activity), ID (intermediate), and DD (highest, ~twice II).

ACE sits at the centre of the renin-angiotensin system (RAS), the body's primary blood pressure regulation mechanism. When blood volume or pressure falls, kidneys release renin, converting angiotensinogen to angiotensin I. ACE then converts angiotensin I to angiotensin II, triggering vasoconstriction, aldosterone release (sodium/water retention), and sustained blood pressure elevation.

Beyond circulating RAS, ACE exists in local tissues (vascular endothelium, heart, kidneys, skeletal muscle, brain), regulating local angiotensin II and influencing vascular tone, cardiac structure, kidney filtration, muscle perfusion, and exercise metabolism.

The I/D polymorphism strongly influences activity: DD genotypes have ~twice the circulating/tissue ACE activity vs II, with ID intermediate. Higher ACE activity increases angiotensin II, promotes higher blood pressure and cardiac hypertrophy, reduces bradykinin, and alters skeletal muscle metabolism/capillarisation. Lower ACE activity has opposite effects (better vascular compliance, enhanced perfusion, improved aerobic metabolism, endurance capacity).

ACE plays a foundational role in blood pressure regulation, cardiovascular structure/function, kidney health, fibrinolytic balance, and exercise performance capacity. Variations in this system have been studied in relation to hypertension, left ventricular hypertrophy, coronary heart disease, kidney disease progression, thrombotic risk, and athletic performance phenotypes.

DD genotype has been associated with increased cardiovascular risk in some populations (context-dependent, often modest effects), including higher hypertension rates, accelerated kidney disease progression in diabetic nephropathy, elevated PAI-1 (reduced fibrinolysis), and greater LVH response to training.

I allele / II genotype shows consistent associations with endurance performance and high-altitude success in multiple analyses, alongside better VO₂max response to training and improved oxygen utilisation. DD may associate with power/sprint performance in some studies, though findings are less consistent than endurance associations with I.

Clinical significance varies: for routine cardiovascular screening, ACE I/D provides modest additional information; for training personalisation, it can be more practically useful; for ACE inhibitor response prediction, evidence is conflicting.

ACE genotype and real-world outcomes don't measure the same thing — they describe different parts of the story:

• ACE phenotype — your actual circulating ACE enzyme activity (blood test) or actual endurance/power performance. This reflects genotype plus training, cardiovascular health, and other factors.
• ACE genotype — the DNA variant you carry at the I/D polymorphism (II, ID, DD). It doesn't change and predicts a substantial portion of ACE activity variability, influencing performance potential.

This matters because training status, cardiovascular health, kidney function, and medications (including ACE inhibitors) significantly modify how genotype shows up in health and performance.

Your ACE genotype doesn't change, but how much it matters depends on modifiable factors. Key influences include:

• Genotype baseline: II (lowest activity), ID (intermediate), DD (highest, ~twice II).
• Training modality: endurance training can amplify I allele advantages; resistance training may amplify hypertrophy response in DD.
• Blood pressure & cardiovascular status: DD risk can be amplified by obesity, high sodium, inactivity, stress; existing disease increases clinical relevance.
• Kidney function/diabetic nephropathy: DD has been associated with faster progression in some contexts; kidney disease can amplify cardiovascular risk.
• Altitude exposure: I allele is associated with better high-altitude performance; DD may see larger decrements.
• Fibrinolysis/thrombotic risk: DD associated with higher PAI-1; lifestyle factors can compound this.
• Age: effects can accumulate over decades.
• Medications: ACE inhibitors/ARBs alter the pathway regardless of genotype.
• Dietary sodium & smoking: can amplify adverse cardiovascular effects; cessation and reduction help regardless of genotype.

Yes — and it's extremely common. Many people with DD or II genotypes never develop clear health problems related to ACE status and only discover genotype through testing. Lifestyle, training, and clinical context often matter more than genotype alone.

Rare genetic conditions affecting ACE (distinct from the common I/D polymorphism) can cause serious disease, but consumer I/D testing does not diagnose those rare disorders.

Unlike blood tests with reference ranges, ACE genotypes aren't “normal” vs “abnormal.” All three are natural variants with trade-offs between cardiovascular regulation and physical performance.

• II (insertion/insertion) — lowest ACE activity; associated with endurance and altitude tolerance; generally lower BP baseline; may have less power/hypertrophy advantage.
• ID (insertion/deletion) — intermediate ACE activity; mixed cardiovascular/performance characteristics.
• DD (deletion/deletion) — highest ACE activity; associated with power/strength potential and greater hypertrophy response; may require more cardiovascular vigilance in some contexts.

From a health perspective, neither genotype is inherently “better” — the goal is understanding implications and optimising modifiable factors.

For DNA-based ACE testing using blood or saliva, fasting is not required because your genetic code doesn't change with meals. If ACE testing is done alongside kidney markers, blood pressure assessment, or a cardiovascular panel, your provider may recommend fasting for those accompanying tests.

Always follow the preparation instructions provided with your specific kit or your healthcare provider.

Managing ACE-related cardiovascular and performance outcomes focuses on optimising modifiable factors and leveraging genetic strengths rather than trying to change genetic baseline. Clinician-guided approaches may include:

• Monitoring and managing blood pressure (particularly for DD carriers), with earlier intervention if hypertension develops (often targeting <130/80 mmHg for cardiovascular protection).
• Kidney surveillance in higher-risk contexts (e.g., diabetes): monitoring creatinine, eGFR, urinary albumin.
• Tailoring exercise programming: emphasising endurance modalities where appropriate; strength/power focus where appropriate; mixed training benefits all.
• Adjusting training volume/intensity/recovery based on response patterns.
• Altitude planning with appropriate acclimatisation.
• Cardiovascular-protective habits: healthy weight, sodium moderation, regular aerobic exercise, stress management, avoiding smoking, moderating alcohol.
• Medication decisions (ACE inhibitors/ARBs) guided by clinical indications; routine genotype-based prescribing isn't currently standard.
• Addressing fibrinolytic risk factors where relevant; lifestyle interventions can help.
• Supporting endothelial/vascular health via diet patterns rich in polyphenols, omega-3s, and nitrate sources.

Because ACE genotype is stable, it can inform long-term training strategies and monitoring protocols, and can be revisited during major health/performance transitions.