What you carry at this position in your DNA and what research says about it.
Cardiovascular and Clot Risk: 8/10 evidence, 20 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): A/A
Higher Risk of Blood Clots and Heart Disease
Carrying two copies of the A allele is associated with elevated PAI-1 levels, which slows down the body's natural ability to dissolve blood clots. This increases the risk of cardiovascular events, deep vein thrombosis, and ischemic stroke.
What this genotype means: Elevated PAI-1 protein levels; Increased risk of coronary artery disease; Higher susceptibility to deep vein thrombosis.
Sample genotype (not yours): A/G
Moderately Increased Risk of Blood Clots
Carrying one copy of the A allele is linked to slightly elevated PAI-1 levels, resulting in a moderate increase in cardiovascular and blood clot risks. It may also slightly reduce response to certain SSRI antidepressants.
What this genotype means: Slightly elevated PAI-1 protein levels; Moderately increased risk of cardiovascular events; Slightly lower response rate to SSRI antidepressants.
Sample genotype (not yours): G/G
Typical Cardiovascular Risk and Lower Clotting Tendency
Carrying two copies of the G allele is associated with lower, typical PAI-1 levels, which supports efficient clot breakdown and maintains baseline cardiovascular risk. However, it is linked to a poorer response to certain SSRI antidepressants.
What this genotype means: Typical PAI-1 protein levels; Baseline risk of coronary artery disease and stroke; Poorer response to citalopram and fluoxetine.
Gene function and biological role
Gene Function: The SERPINE1 gene encodes plasminogen activator inhibitor-1 (PAI-1), a crucial protein that regulates the body's ability to dissolve blood clots [1]. PAI-1 acts as the primary inhibitor of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which are responsible for converting plasminogen into active plasmin to break down fibrin clots [1]. When PAI-1 levels are elevated, the natural clot-clearing process is slowed down, which can lead to an accumulation of fibrin and increase the risk of thrombosis [1]. Conversely, a deficiency in PAI-1 can lead to abnormal bleeding tendencies [1]. Beyond its role in cardiovascular health, PAI-1 expression is also influenced by cellular stress and has been implicated in tissue remodeling, metabolic syndrome, and neurological pathways [2].
Variant Impact: The rs2227631 variant is a single nucleotide polymorphism located in the promoter region of the SERPINE1 gene, often referred to as the -844 G/A polymorphism [3]. This genetic change directly influences the transcription rate of the gene, thereby altering the circulating levels of the PAI-1 protein in the bloodstream [3]. The minor A allele is associated with increased promoter activity, leading to higher circulating levels of PAI-1 and a subsequent reduction in fibrinolytic activity [3]. Because it is in tight linkage disequilibrium with the functional 4G/5G promoter polymorphism, rs2227631 serves as a strong genetic marker for elevated cardiovascular and thromboembolic risk [4].
Key Insight: The same genetic variant that increases the risk of cardiovascular events by elevating blood-clotting proteins also appears to influence how the brain responds to common SSRI antidepressants.
Location: SERPINE1. Chromosome 7 · 7q22.1 · 101.1 Mb
Estimated prevalence by population
Global 23.7%; European 34.7%; African 7.2%; East Asian 16.1%; South Asian 25.5%; Americas 14.6%; Ashkenazi 29.8%; Finnish 30.2%; Middle Eastern 16.4%; Amish 52.6%.
Estimated AA genotype frequency.
Global 45.9%; European 48.4%; African 39.2%; East Asian 48.1%; South Asian 50.0%; Americas 47.2%; Ashkenazi 49.6%; Finnish 49.5%; Middle Eastern 48.2%; Amish 39.8%.
Estimated AG genotype frequency.
Global 30.4%; European 16.9%; African 53.6%; East Asian 35.8%; South Asian 24.5%; Americas 38.1%; Ashkenazi 20.6%; Finnish 20.3%; Middle Eastern 35.4%; Amish 7.5%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Coagulation & Clotting
PAI-1 Protein Levels. Evidence: 8/10. Source: PMID 22990020. Elevated Levels.
Venous Thromboembolism. Evidence: 6/10. Source: PMID 35285134. Increased Risk.
Heart Disease
Coronary Artery Disease. Evidence: 6/10. Source: PMID 35285134. Increased Risk.
Stroke
Ischemic Stroke. Evidence: 6/10. Source: PMID 35285134. Increased Risk.
Pharmacogenomics
Antidepressant & Psychiatric Drug Response
Antidepressant Response. Evidence: 5/10. Source: PMID 18794724. Typical Response.
Showing effects for A/G genotype
PAI-1 Protein Levels. Evidence: 8/10. Source: PMID 22990020. Slightly Elevated.
Venous Thromboembolism. Evidence: 6/10. Source: PMID 35285134. Slightly Increased.
Coronary Artery Disease. Evidence: 6/10. Source: PMID 35285134. Slightly Increased.
Ischemic Stroke. Evidence: 6/10. Source: PMID 35285134. Slightly Increased.
Antidepressant Response. Evidence: 5/10. Source: PMID 18794724. Poorer Response.
Showing effects for G/G genotype
PAI-1 Protein Levels. Evidence: 8/10. Source: PMID 22990020. Typical Levels.
Venous Thromboembolism. Evidence: 6/10. Source: PMID 35285134. Typical Risk.
Coronary Artery Disease. Evidence: 6/10. Source: PMID 35285134. Typical Risk.
Ischemic Stroke. Evidence: 6/10. Source: PMID 35285134. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
This genotype is characterized by having two copies of the promoter-activating A allele, which leads to significantly higher circulating levels of plasminogen activator inhibitor-1 (PAI-1) [1]. Elevated PAI-1 acts as a brake on the fibrinolytic system, making it more difficult for the body to break down blood clots once they form [1]. Consequently, clinical studies have linked this genotype to an increased risk of coronary artery disease, venous thromboembolism, and ischemic stroke [2]. The reduced rate of clot clearance can also impact blood flow in small vessels, which has been associated with conditions like osteonecrosis of the femoral head [3]. Interestingly, while this genotype presents cardiovascular challenges, some research suggests that individuals with the A/A genotype may have a more favorable response to certain SSRI antidepressants like citalopram and fluoxetine compared to G allele carriers [4].
Elevated PAI-1 protein levels; Increased risk of coronary artery disease; Higher susceptibility to deep vein thrombosis; Increased risk of ischemic stroke.
Sample genotype: AG (Heterozygous)
Having one copy of the A allele and one copy of the G allele typically results in intermediate circulating levels of PAI-1 [1]. While the risk is not as pronounced as in individuals with two copies of the A allele, there is still a moderate reduction in the efficiency of the body's clot-dissolving mechanisms [1]. This intermediate state is associated with a slightly elevated risk of coronary artery disease, venous thromboembolism, and ischemic stroke compared to the G/G baseline [2]. Additionally, the presence of the G allele in this genotype has been associated with a lower likelihood of achieving a full therapeutic response to selective serotonin reuptake inhibitors (SSRIs) such as citalopram and fluoxetine [3]. Managing overall cardiovascular health through lifestyle factors remains an important strategy to mitigate these moderate genetic risks.
Slightly elevated PAI-1 protein levels; Moderately increased risk of cardiovascular events; Slightly lower response rate to SSRI antidepressants.
Sample genotype: GG (Homozygous)
This genotype is associated with lower promoter activity and typical circulating levels of PAI-1, allowing the body's natural clot-dissolving processes to function efficiently [1]. By maintaining standard fibrinolytic activity, individuals with this genotype do not experience the elevated risks of coronary artery disease, deep vein thrombosis, or ischemic stroke associated with the A allele [2]. This baseline clotting profile supports overall vascular health and reduces the likelihood of clot-related complications [2]. On the other hand, pharmacogenomic data indicates that the G/G genotype is associated with a poorer therapeutic response to SSRI antidepressants, specifically citalopram and fluoxetine, meaning alternative treatments or adjusted strategies might be discussed with a doctor if depression treatment is needed [3].
Typical PAI-1 protein levels; Baseline risk of coronary artery disease and stroke; Poorer response to citalopram and fluoxetine.
Variants with shared genetic architecture
rs1799889 · SERPINE1 Gene · Chr 7 · Cardiovascular and Clotting Risk
rs10886430 · GRK5 Gene · Chr 10 · Blood Clot Risk
rs5030062 · KNG1 Gene · Chr 3 · Stroke and Blood Clot Risk
Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head.
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