What you carry at this position in your DNA and what research says about it.
Heart and Vascular Health: 5/10 evidence, 57 publications.
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Sample genotype (not yours): C/C
Higher Cardiovascular Risk
This genotype is linked to lower nitric oxide levels, which can increase the risk of high blood pressure and heart disease.
What this genotype means: Lower baseline nitric oxide production; Increased risk of resistant hypertension; Highly responsive to aerobic exercise.
Sample genotype (not yours): C/T
Slightly Elevated Vascular Risk
Carrying one copy of the C allele may slightly lower nitric oxide levels, presenting a mild increase in cardiovascular susceptibility.
What this genotype means: Moderately reduced nitric oxide levels; Slightly increased susceptibility to migraines; Favorable blood pressure response to exercise.
Sample genotype (not yours): T/T
Typical Cardiovascular Risk
This genotype supports standard nitric oxide levels, helping to maintain typical blood vessel function and lower cardiovascular risk.
What this genotype means: Standard nitric oxide production; Lower risk of metabolic syndrome; Typical response to aerobic exercise.
Gene function and biological role
Gene Function: The NOS3 gene encodes endothelial nitric oxide synthase, an enzyme vital for cardiovascular health [1]. It produces nitric oxide, a key signaling molecule that relaxes blood vessels, regulates blood pressure, and maintains healthy blood flow [1]. Healthy nitric oxide production prevents blood vessels from narrowing and protects against plaque buildup [2]. Variations in this gene can alter enzyme levels, directly impacting vascular tone and overall cardiovascular resilience [2].
Variant Impact: The rs2070744 variant is located in the promoter region of the NOS3 gene and directly influences enzyme production [3]. Carrying the C allele increases the binding of a repressor protein, which reduces gene transcription and lowers nitric oxide levels [4]. Conversely, the T allele allows for typical promoter activity and standard nitric oxide levels [4]. This difference in nitric oxide availability influences blood pressure, cardiovascular risk, and response to exercise [3] [4].
Key Insight: The C allele reduces nitric oxide production by approximately half, but carriers of this allele actually experience a much greater drop in blood pressure from aerobic exercise than non-carriers.
Location: NOS3. Chromosome 7 · 7q36.1 · 151.0 Mb
Estimated prevalence by population
Global 10.0%; European 15.2%; African 2.5%; East Asian 1.2%; South Asian 5.2%; Americas 9.7%; Ashkenazi 12.6%; Finnish 12.4%; Middle Eastern 13.7%; Amish 8.1%.
Estimated CC genotype frequency.
Global 39.8%; European 47.6%; African 26.7%; East Asian 19.6%; South Asian 35.3%; Americas 42.9%; Ashkenazi 45.8%; Finnish 45.6%; Middle Eastern 46.7%; Amish 40.7%.
Estimated CT genotype frequency.
Global 50.2%; European 37.2%; African 70.7%; East Asian 79.1%; South Asian 59.5%; Americas 47.4%; Ashkenazi 41.6%; Finnish 42.0%; Middle Eastern 39.6%; Amish 51.3%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Heart Disease
Heart Disease. Evidence: 3/10. Source: PMID 22470539. Increased Risk.
Metabolic Syndrome & Insulin Resistance
Metabolic Syndrome. Evidence: 5/10. Source: PMID 29907847. Increased Risk.
Cancer & Oncology
Prostate Cancer
Prostate Cancer. Evidence: 3/10. Source: PMID 25164276. Increased Risk.
Neurology & Mental Health
Headache & Migraine
Migraine. Evidence: 4/10. Source: PMID 31792366. Increased Risk.
Lifestyle, Fitness & Aging
Physical Performance & Endurance
Exercise Blood Pressure Response. Evidence: 3/10. Source: PMID 19155013. Stronger BP Drop.
Showing effects for C/T genotype
Heart Disease. Evidence: 3/10. Source: PMID 22470539. Slightly Increased.
Metabolic Syndrome. Evidence: 5/10. Source: PMID 29907847. Typical Risk.
Prostate Cancer. Evidence: 3/10. Source: PMID 25164276. Typical Risk.
Migraine. Evidence: 4/10. Source: PMID 31792366. Slightly Increased.
Showing effects for T/T genotype
Heart Disease. Evidence: 3/10. Source: PMID 22470539. Typical Risk.
Metabolic Syndrome. Evidence: 5/10. Source: PMID 29907847. Lower Risk.
Migraine. Evidence: 4/10. Source: PMID 31792366. Typical Risk.
Exercise Blood Pressure Response. Evidence: 3/10. Source: PMID 19155013. Typical BP Drop.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele is associated with a significant reduction in the transcription of the NOS3 gene, leading to lower circulating nitric oxide levels [1]. This reduction in nitric oxide can impair the ability of blood vessels to relax, potentially contributing to higher blood pressure and arterial stiffness [1]. Clinical studies have linked this genotype to an increased risk of resistant hypertension and cardiovascular complications [2]. However, individuals with this genotype respond exceptionally well to the blood-pressure-lowering benefits of regular aerobic exercise [1]. They may also show a more favorable response to specific medications like enalapril and sildenafil [2].
Lower baseline nitric oxide production; Increased risk of resistant hypertension; Highly responsive to aerobic exercise.
Sample genotype: CT (Heterozygous)
Having one copy of the C allele puts individuals in an intermediate category for nitric oxide production [1]. While they do not experience the full reduction in gene expression seen in the C/C genotype, they may still have slightly lower baseline nitric oxide levels than those with the T/T genotype [1]. This mild reduction is associated with a slightly higher susceptibility to vascular issues, including migraines and elevated blood pressure under stress [2]. On the positive side, carrying the C allele means these individuals still benefit from enhanced blood pressure reduction following aerobic exercise [1]. They also tend to respond well to certain vascular medications [2].
Moderately reduced nitric oxide levels; Slightly increased susceptibility to migraines; Favorable blood pressure response to exercise.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele is the most common genetic profile and is associated with typical promoter activity of the NOS3 gene [1]. This supports standard levels of nitric oxide production, which helps keep blood vessels flexible and healthy [1]. Individuals with this genotype generally have a lower risk of developing metabolic syndrome and resistant hypertension compared to C allele carriers [2]. While they do not get the extra-strong blood pressure drop from aerobic exercise seen in C carriers, they maintain a stable baseline of vascular health [1]. Their risk for conditions like migraines and prostate cancer progression is also at the typical population baseline [2].
Standard nitric oxide production; Lower risk of metabolic syndrome; Typical response to aerobic exercise.
Variants with shared genetic architecture
rs3918226 · NOS3 Gene · Chr 7 · Cardiovascular Risk
rs891511 · NOS3 Gene · Chr 7 · Blood Pressure
rs1799983 · NOS3 Gene · Chr 7 · Heart and Vascular Health
Association between endothelial nitric oxide synthase (NOS3) rs2070744 and the risk for migraine.
eNOS and BDKRB2 genotypes affect the antihypertensive responses to enalapril.
Content updated August 2026.
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