What you carry at this position in your DNA and what research says about it.
Cardiovascular Risk: 10/10 evidence, 37 publications.
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Sample genotype (not yours): C/C
Typical Blood Pressure and Heart Risk
Blood vessels produce normal levels of nitric oxide, supporting healthy circulation. This helps maintain typical blood pressure and a lower baseline risk of heart disease.
What this genotype means: Typical blood pressure levels; Typical risk of coronary artery disease; Slightly higher risk of allergic rhinitis.
Sample genotype (not yours): C/T
Slightly Higher Blood Pressure and Heart Risk
A single copy of the T allele is associated with slightly reduced nitric oxide production. This can lead to mild increases in blood pressure and a modest rise in cardiovascular risk.
What this genotype means: Slightly higher blood pressure; Modestly increased risk of heart disease; Slightly lower risk of allergic rhinitis.
Sample genotype (not yours): T/T
Higher Blood Pressure and Heart Risk
Two copies of the T allele are linked to significantly lower nitric oxide levels. This increases the risk of high blood pressure, heart disease, and reduced kidney function.
What this genotype means: Higher risk of hypertension; Increased risk of coronary artery disease; Lower risk of allergic rhinitis.
Gene function and biological role
Gene Function: Endothelial nitric oxide synthase 3 is an enzyme encoded by the NOS3 gene that plays a fundamental role in maintaining vascular health [1]. It synthesizes nitric oxide, a crucial signaling molecule that relaxes blood vessels, regulates blood pressure, and prevents platelets from sticking to vessel walls [2]. Proper production of nitric oxide is essential for protecting against atherosclerosis and maintaining healthy blood flow throughout the body [1]. Reduced activity of this enzyme can lead to endothelial dysfunction, which is a key early step in the development of cardiovascular diseases [2].
Variant Impact: The rs3918226 variant is located in the NOS3 gene and influences how efficiently the gene is transcribed into the active enzyme [1]. Carrying the T allele is associated with decreased expression of the gene, particularly in arterial tissues, leading to lower levels of nitric oxide [1]. This reduction in nitric oxide bioavailability impairs the ability of blood vessels to dilate properly, resulting in higher systemic blood pressure [3]. Over time, this lack of vascular protection increases the risk of developing coronary artery disease and other cardiovascular complications [2].
Key Insight: Although the T allele increases blood pressure and heart disease risk, it actually lowers the risk of developing allergic rhinitis.
Location: NOS3. Chromosome 7 · 7q36.1 · 151.0 Mb
Estimated prevalence by population
Global 89.2%; European 84.2%; African 97.0%; East Asian > 99.9%; South Asian 98.1%; Americas 87.1%; Ashkenazi 86.3%; Finnish 84.9%; Middle Eastern 87.5%; Amish 93.7%.
Estimated CC genotype frequency.
Global 10.4%; European 15.2%; African 3.0%; East Asian < 0.1%; South Asian 1.8%; Americas 12.5%; Ashkenazi 13.2%; Finnish 14.5%; Middle Eastern 12.1%; Amish 6.2%.
Estimated CT genotype frequency.
Global 0.4%; European 0.7%; African < 0.1%; East Asian < 0.1%; South Asian < 0.1%; Americas 0.4%; Ashkenazi 0.5%; Finnish 0.6%; Middle Eastern 0.4%; Amish 0.1%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Heart Disease
Coronary Artery Disease. Evidence: 8/10. Source: PMID 36474045. Typical Risk.
Hypertension
Blood Pressure. Evidence: 10/10. Source: PMID 38689001. Typical.
Organ Systems
Kidney Function & Disease
Kidney Function. Evidence: 8/10. Source: PMID 34272381. Typical.
Immunity & Inflammation
Allergy & Hypersensitivity
Allergic Rhinitis. Evidence: 6/10. Source: PMID 31361310. ~1.07x Increased Risk.
Showing effects for C/T genotype
Coronary Artery Disease. Evidence: 8/10. Source: PMID 36474045. ~1.12x Increased Risk.
Blood Pressure. Evidence: 10/10. Source: PMID 38689001. Slightly Higher.
Kidney Function. Evidence: 8/10. Source: PMID 34272381. Slightly Reduced.
Allergic Rhinitis. Evidence: 6/10. Source: PMID 31361310. Typical Risk.
Showing effects for T/T genotype
Coronary Artery Disease. Evidence: 8/10. Source: PMID 36474045. Increased Risk.
Blood Pressure. Evidence: 10/10. Source: PMID 38689001. Higher.
Kidney Function. Evidence: 8/10. Source: PMID 34272381. Reduced.
Allergic Rhinitis. Evidence: 6/10. Source: PMID 31361310. Lower Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Maintaining optimal nitric oxide production is a key feature of this genotype, which supports the natural relaxation of blood vessels [1]. Because nitric oxide levels remain typical, the vascular walls are better protected against the inflammatory processes that lead to plaque buildup [2]. Studies show that individuals with this genotype have a lower risk of developing coronary artery disease and myocardial infarction compared to those carrying the T allele [2]. Additionally, healthy nitric oxide levels support optimal blood flow to the kidneys, maintaining typical glomerular filtration rates [3]. While there is a very slight increase in the risk of allergic rhinitis, the overall cardiovascular profile remains highly favorable [4]. This natural vascular protection helps maintain healthy circulation throughout the body over a lifetime. Regular physical activity can further enhance this enzyme's activity, boosting cardiovascular resilience even more. Consequently, maintaining a balanced diet and active lifestyle works in harmony with this genetic baseline.
Typical blood pressure levels; Typical risk of coronary artery disease; Slightly higher risk of allergic rhinitis.
Sample genotype: CT (Heterozygous)
A single copy of the T allele is linked to a moderate reduction in the expression of the endothelial nitric oxide synthase enzyme [1]. This reduction can limit the bioavailability of nitric oxide, making it slightly harder for blood vessels to dilate efficiently under stress [2]. Large-scale genetic studies have associated this genotype with a modest increase in both systolic and diastolic blood pressure [2]. There is also a small but measurable increase in the risk of coronary artery disease and heart attacks [3]. Kidney function may also be slightly affected, as lower nitric oxide can subtly reduce the glomerular filtration rate [4]. However, the risk of allergic rhinitis is slightly lower compared to the common C/C genotype [5]. Managing cardiovascular health through lifestyle choices becomes more important when this genetic predisposition is present. Simple habits like reducing sodium intake and engaging in aerobic exercise can help counteract the slight reduction in nitric oxide. These proactive steps support long-term arterial flexibility and overall heart health.
Slightly higher blood pressure; Modestly increased risk of heart disease; Slightly lower risk of allergic rhinitis.
Sample genotype: TT (Homozygous)
Possessing two copies of the T allele leads to the lowest predicted expression of the endothelial nitric oxide synthase enzyme [1]. This significant drop in nitric oxide production impairs the endothelium's ability to regulate vascular tone, leading to stiffer arteries [2]. Consequently, this genotype is strongly associated with elevated systolic and diastolic blood pressure, as well as an increased risk of clinical hypertension [2]. The risk of coronary artery disease and myocardial infarction is also notably higher in this group [3]. Furthermore, reduced nitric oxide levels can compromise renal blood flow, leading to lower glomerular filtration rates and higher creatinine levels [4]. On the positive side, this genotype appears to offer some protection against allergic rhinitis [5]. Focusing on cardiovascular wellness is highly beneficial for individuals with this genetic profile. Adopting a heart-healthy diet rich in antioxidants and nitrates, such as leafy greens, can help support alternative pathways for nitric oxide production. Regular cardiovascular exercise is also a powerful tool to stimulate the blood vessels and promote better circulation.
Higher risk of hypertension; Increased risk of coronary artery disease; Lower risk of allergic rhinitis.
Variants with shared genetic architecture
rs891511 · NOS3 Gene · Chr 7 · Blood Pressure
rs1799983 · NOS3 Gene · Chr 7 · Heart and Vascular Health
rs2070744 · NOS3 Gene · Chr 7 · Heart and Vascular Health
Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
Content updated August 2026.
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