What you carry at this position in your DNA and what research says about it.
Blood Pressure and Brain: 6/10 evidence, 28 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): T/T
Lower Alzheimer's Risk but Higher Depression Risk
This genotype is linked to slightly higher blood pressure and a reduced risk of Alzheimer's disease, but carries an increased susceptibility to major depression.
What this genotype means: Lower risk of Alzheimer's disease; Slightly higher systolic blood pressure; Higher risk of major depression.
Sample genotype (not yours): A/A
Elevated Alzheimer's Risk but Slightly Lower Blood Pressure
This genotype is associated with slightly lower systolic blood pressure and an increased risk of Alzheimer's disease, but a lower risk of major depression.
What this genotype means: Slightly lower systolic blood pressure; Increased risk of late-onset Alzheimer's; Lower risk of major depression.
Sample genotype (not yours): T/A
Typical Blood Pressure and Balanced Brain Health Risks
Carrying one copy of each allele results in intermediate, typical risks for blood pressure, Alzheimer's disease, and depression.
What this genotype means: Typical blood pressure levels; Average risk of Alzheimer's disease; Slightly better response to losartan.
Gene function and biological role
Gene Function: The ACE gene encodes the angiotensin I converting enzyme, a key regulator of the renin-angiotensin system that controls blood pressure and fluid balance [1]. Beyond its cardiovascular role, ACE is highly expressed in the brain, where it acts as an amyloid-degrading enzyme that helps clear toxic beta-amyloid plaques [2]. This dual functionality creates a biological trade-off: higher ACE levels can elevate blood pressure but protect against cognitive decline [1] [2]. Pharmacologically, ACE is the primary target for widely prescribed blood pressure medications known as ACE inhibitors [1].
Variant Impact: The rs4291 variant is located in the promoter region of the ACE gene, directly influencing how much of the enzyme is produced [2]. The major A allele is associated with lower cortical ACE expression in the brain, which reduces the clearance of beta-amyloid [2]. Conversely, the minor T allele increases ACE expression, leading to higher circulating enzyme levels [3]. This promoter change alters both systemic blood pressure regulation and susceptibility to neurodegenerative and mood disorders [2] [3].
Key Insight: The same genetic variant that helps protect your brain from Alzheimer's disease by clearing amyloid plaques can also increase your risk of major depression and raise your sensitivity to aspirin.
Location: ACE. Chromosome 17 · 17q23.3 · 63.5 Mb
Estimated prevalence by population
Global 13.5%; European 14.4%; African 11.9%; East Asian 13.0%; South Asian 14.0%; Americas 10.4%; Ashkenazi 19.6%; Finnish 14.8%; Middle Eastern 20.4%; Amish 18.2%.
Estimated TT genotype frequency.
Global 46.3%; European 47.1%; African 45.2%; East Asian 46.1%; South Asian 46.8%; Americas 43.7%; Ashkenazi 49.4%; Finnish 47.3%; Middle Eastern 49.5%; Amish 48.9%.
Estimated TA genotype frequency.
Global 40.3%; European 38.5%; African 42.8%; East Asian 40.9%; South Asian 39.1%; Americas 46.0%; Ashkenazi 31.0%; Finnish 37.9%; Middle Eastern 30.1%; Amish 32.8%.
Estimated AA genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Hypertension
Blood Pressure. Evidence: 6/10. Source: PMID 30578418. Slightly Higher SBP.
Neurology & Mental Health
Neurodegenerative Diseases
Alzheimer's Disease. Evidence: 4/10. Source: PMID 24851853. Lower Risk.
Mood Disorders
Depression. Evidence: 3/10. Source: PMID 16924268. Higher Risk.
Pharmacogenomics
Cardiovascular Drug Response
Losartan Response. Evidence: 5/10. Source: PMID 38551694. Stronger Response.
Adverse Drug Reactions
Aspirin Sensitivity. Evidence: 5/10. Source: PMID 18727619. Increased Risk.
Showing effects for A/A genotype
Blood Pressure. Evidence: 6/10. Source: PMID 30578418. Slightly Lower SBP.
Alzheimer's Disease. Evidence: 4/10. Source: PMID 24851853. Higher Risk.
Depression. Evidence: 3/10. Source: PMID 16924268. Lower Risk.
Losartan Response. Evidence: 5/10. Source: PMID 38551694. Typical Response.
Aspirin Sensitivity. Evidence: 5/10. Source: PMID 18727619. Typical Risk.
Showing effects for T/A genotype
Blood Pressure. Evidence: 6/10. Source: PMID 30578418. Typical SBP.
Alzheimer's Disease. Evidence: 4/10. Source: PMID 24851853. Typical Risk.
Depression. Evidence: 3/10. Source: PMID 16924268. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Having two copies of the T allele is associated with higher cortical expression of the ACE enzyme, which actively degrades toxic amyloid-beta plaques in the brain [1]. This higher expression provides a protective effect against late-onset Alzheimer's disease [1]. Additionally, this genotype is linked to slightly higher systolic blood pressure and a highly favorable response to the blood pressure medication losartan [2] [3]. However, the T allele is also associated with hyperactivity of the hypothalamic-pituitary-adrenocortical axis, which increases cortisol levels and elevates the risk of major depression [4]. Finally, individuals with this genotype may have a higher risk of aspirin intolerance, particularly if they have asthma [5].
Lower risk of Alzheimer's disease; Slightly higher systolic blood pressure; Higher risk of major depression; Better response to losartan.
Sample genotype: AA (Homozygous)
Having two copies of the A allele is linked to lower expression of the ACE enzyme in the brain's cortex [1]. Because ACE plays a vital role in breaking down amyloid-beta, this reduced expression is associated with an increased risk and earlier onset of late-onset Alzheimer's disease [1]. Systemically, this reduced ACE activity is associated with modestly lower systolic blood pressure, so this genotype carries a genuine trade-off: higher Alzheimer's risk alongside slightly lower blood pressure [2]. On the positive side, this genotype is protective against major depression, as it is linked to lower cortisol levels and reduced stress-system activity [3]. Regarding medications, individuals with this genotype may experience a typical response to losartan but have a lower risk of aspirin-induced intolerance [4] [5].
Slightly lower systolic blood pressure; Increased risk of late-onset Alzheimer's; Lower risk of major depression; Typical response to losartan.
Sample genotype: TA (Heterozygous)
Having the heterozygous T/A genotype provides a balanced genetic profile with average baseline risks across most associated traits [1]. Blood pressure levels and the risk of developing late-onset Alzheimer's disease are generally near the population average [1] [2]. While the single T allele slightly increases the risk of major depression compared to the A/A genotype, the effect is modest [3]. On the medication front, this genotype is still associated with a favorable response to the antihypertensive drug losartan [4]. However, there remains a slightly elevated risk of aspirin intolerance that carriers should be aware of [5].
Typical blood pressure levels; Average risk of Alzheimer's disease; Slightly better response to losartan; Slightly higher risk of aspirin intolerance.
Variants with shared genetic architecture
rs4311 · ACE Gene · Chr 17 · Diabetic Kidney Risk
rs4343 · ACE Gene · Chr 17 · Blood Pressure and Kidney Risk
rs1799752 · ACE Gene · Chr 17 · Blood Pressure and Fitness
Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com