What you carry at this position in your DNA and what research says about it.
Hypertension Risk: 7/10 evidence, 21 publications.
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Sample genotype (not yours): T/T
Higher Blood Pressure and Hypertension Risk
Two copies of the T allele are associated with higher systolic and diastolic blood pressure. This genetic profile also increases the risk of developing hypertension and having elevated uric acid levels.
What this genotype means: Higher risk of hypertension; Elevated systolic and diastolic blood pressure; Increased uric acid levels.
Sample genotype (not yours): A/A
Lower Blood Pressure but Higher Cardiovascular Risk
Two copies of the A allele are linked to lower blood pressure and a reduced risk of hypertension. However, this profile is also associated with a higher risk of coronary artery disease.
What this genotype means: Lower risk of hypertension; Reduced blood pressure levels; Higher risk of coronary artery disease.
Sample genotype (not yours): T/A
Typical Blood Pressure and Balanced Metabolic Profile
Inheriting one T allele and one A allele results in an intermediate metabolic profile. Blood pressure, uric acid levels, and cardiovascular risks are generally close to the population average.
What this genotype means: Typical blood pressure levels; Average risk of hypertension; Balanced cardiovascular risk profile.
Gene function and biological role
Gene Function: The HECTD4 gene encodes an E3 ubiquitin protein ligase, an enzyme involved in tagging other proteins for degradation within cells. This gene plays a crucial role in metabolic regulation, insulin sensitivity, and glucose homeostasis. Variations in HECTD4 have been strongly linked to blood pressure regulation and the development of hypertension [1]. Research also connects this gene to liver enzyme levels, lipid metabolism, and uric acid clearance [2]. In East Asian populations, HECTD4 is a major genetic determinant of metabolic syndrome and cardiovascular health [3].
Variant Impact: The rs11066280 variant is an intron variant located within the HECTD4 gene on chromosome 12. This genetic change influences the expression or splicing of the HECTD4 protein, thereby altering downstream metabolic pathways. The major T allele is highly prevalent globally but shows a distinct distribution, being particularly common in East Asian populations where it strongly influences blood pressure [4]. Conversely, the minor A allele is associated with lower blood pressure but may slightly increase the risk of other conditions like coronary artery disease [5]. Understanding this variant helps clarify the genetic trade-offs between blood pressure control and cardiovascular risk [6].
Key Insight: This variant represents a classic genetic trade-off where the same genetic code that protects against high blood pressure can slightly increase the risk of coronary artery disease.
Location: HECTD4. Chromosome 12 · 12q24.13 · 112.4 Mb
Estimated prevalence by population
Global 98.2%; European 100.0%; African 99.7%; East Asian 55.5%; South Asian 98.9%; Americas 99.8%; Ashkenazi 99.9%; Middle Eastern 100.0%; Amish 100.0%.
Estimated TT genotype frequency.
Global 1.6%; European 0.0%; African 0.3%; East Asian 38.0%; South Asian 1.1%; Americas 0.2%; Ashkenazi 0.1%; Middle Eastern 0.0%; Amish 0.0%.
Estimated TA genotype frequency.
Global 0.2%; European 0.0%; African < 0.1%; East Asian 6.5%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi < 0.1%; Middle Eastern 0.0%; Amish 0.0%.
Estimated AA genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Hypertension
Hypertension. Evidence: 7/10. Source: PMID 25249183. Increased Risk.
Blood Pressure. Evidence: 8/10. Source: PMID 21572416. Higher.
Gout & Uric Acid
Uric Acid Levels. Evidence: 6/10. Source: PMID 29124443. Higher.
Heart Disease
Coronary Artery Disease. Evidence: 5/10. Source: PMID 22751097. Lower Risk.
Lipids & Cholesterol
Triglycerides. Evidence: 7/10. Source: PMID 26582766. Higher.
Cancer & Oncology
Gastrointestinal Cancers
Esophageal Cancer. Evidence: 5/10. Source: PMID 21642993. Lower Risk.
Organ Systems
Liver Function & Disease
Liver Enzyme Levels. Evidence: 6/10. Source: PMID 21909109. Lower.
Showing effects for A/A genotype
Hypertension. Evidence: 7/10. Source: PMID 25249183. Lower Risk.
Blood Pressure. Evidence: 8/10. Source: PMID 21572416. Lower.
Uric Acid Levels. Evidence: 6/10. Source: PMID 29124443. Lower.
Coronary Artery Disease. Evidence: 5/10. Source: PMID 22751097. Increased Risk.
Triglycerides. Evidence: 7/10. Source: PMID 26582766. Lower.
Esophageal Cancer. Evidence: 5/10. Source: PMID 21642993. Increased Risk.
Liver Enzyme Levels. Evidence: 6/10. Source: PMID 21909109. Higher.
Showing effects for T/A genotype
Hypertension. Evidence: 7/10. Source: PMID 25249183. Typical.
Blood Pressure. Evidence: 8/10. Source: PMID 21572416. Typical.
Uric Acid Levels. Evidence: 6/10. Source: PMID 29124443. Typical.
Coronary Artery Disease. Evidence: 5/10. Source: PMID 22751097. Typical.
Triglycerides. Evidence: 7/10. Source: PMID 26582766. Typical.
Esophageal Cancer. Evidence: 5/10. Source: PMID 21642993. Typical.
Liver Enzyme Levels. Evidence: 6/10. Source: PMID 21909109. Typical.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Having the T/T genotype is associated with a significantly higher risk of hypertension and elevated blood pressure [1]. Research indicates that this genotype raises systolic blood pressure by approximately 1.45 mmHg and diastolic blood pressure by nearly 1 mmHg [2]. Additionally, it is linked to higher serum uric acid levels, which can increase the susceptibility to gout [3]. On the metabolic front, this genotype is associated with higher triglyceride levels and body weight [4]. However, there is a notable genetic trade-off, as the T/T genotype is associated with a lower risk of coronary artery disease [5]. It also correlates with a lower risk of esophageal cancer and lower levels of the liver enzyme alanine aminotransferase [6]. Managing blood pressure through diet and exercise is particularly beneficial for individuals with this profile.
Higher risk of hypertension; Elevated systolic and diastolic blood pressure; Increased uric acid levels; Lower risk of coronary artery disease.
Sample genotype: AA (Homozygous)
The A/A genotype is strongly associated with lower systolic and diastolic blood pressure, offering natural protection against hypertension [1]. This genetic profile also correlates with lower serum uric acid levels, reducing the likelihood of developing gout [2]. Additionally, individuals with this genotype tend to have lower triglyceride levels and lower body weight [3]. However, this genotype presents a distinct cardiovascular trade-off, as it is linked to an increased risk of coronary artery disease [4]. It is also associated with higher levels of the liver enzyme alanine aminotransferase, which can indicate altered liver metabolism [5]. Furthermore, research has connected this genotype to an increased risk of esophageal cancer [6].
Lower risk of hypertension; Reduced blood pressure levels; Higher risk of coronary artery disease; Elevated liver enzyme levels.
Sample genotype: TA (Heterozygous)
The T/A genotype represents a balanced genetic profile with intermediate risks across several metabolic and cardiovascular traits. Blood pressure levels and the risk of developing hypertension are typically near the population average [1]. Uric acid levels and the risk of gout are also intermediate, showing neither the elevation of the T/T genotype nor the reduction of the A/A genotype [2]. Similarly, liver enzyme levels and triglyceride measurements tend to be typical [3]. The trade-off between blood pressure and coronary artery disease risk is balanced in this heterozygous state [4]. This genotype does not significantly elevate the risk of esophageal cancer compared to the minor allele homozygote [5]. Overall, maintaining a standard healthy lifestyle supports optimal cardiovascular health for individuals with this profile.
Typical blood pressure levels; Average risk of hypertension; Balanced cardiovascular risk profile.
Variants with shared genetic architecture
rs11066188 · HECTD4 Gene · Chr 12 · Heart and Weight Health
rs2074356 · HECTD4 Gene · Chr 12 · Esophageal Cancer Risk
rs10857147 · FGF5 Gene · Chr 4 · Blood Pressure
Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.
Content updated August 2026.
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