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rs2266788 (APOA5)

What you carry at this position in your DNA and what research says about it.

Triglyceride Levels: 10/10 evidence, 16 publications.

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Sample genotype (not yours): G/G

Significantly Higher Triglycerides and Cardiovascular Risk

Inheriting two copies of the minor G allele is associated with elevated blood triglycerides and lower HDL cholesterol. This combination can increase the risk of developing coronary artery disease and metabolic syndrome.

What this genotype means: Elevated blood triglycerides; Lower HDL cholesterol; Increased risk of coronary artery disease.

Sample genotype (not yours): A/A

Typical Triglycerides and Standard Cardiovascular Risk

Carrying two copies of the major A allele is associated with normal triglyceride clearance and typical HDL cholesterol levels. This genotype represents the baseline genetic risk for heart health.

What this genotype means: Typical blood triglyceride levels; Standard HDL and LDL cholesterol levels; Baseline risk of coronary artery disease.

Sample genotype (not yours): G/A

Moderately Higher Triglycerides and Cardiovascular Risk

Carrying one copy of the minor G allele is linked to moderately elevated triglycerides and slightly lower HDL cholesterol. This profile can modestly increase the lifetime risk of cardiovascular issues.

What this genotype means: Moderately elevated triglycerides; Slightly lower HDL cholesterol; Modestly increased risk of coronary artery disease.

About APOA5

Gene function and biological role

Gene Function: The ZPR1 gene encodes a zinc finger protein that is essential for cell growth and interacts with translation machinery. It lies in close physical proximity to the APOA5 gene on chromosome 11, forming a highly active lipid-regulating gene cluster [1]. APOA5 encodes apolipoprotein A-V, a specialized protein produced in the liver that plays a critical role in clearing triglyceride-rich lipoproteins from the bloodstream [2]. This protein works by accelerating the breakdown of circulating fats through the activation of lipoprotein lipase [3]. Because of this close genetic linkage, variations in this region are among the strongest known genetic determinants of blood lipid levels in humans [4].

Variant Impact: Located in the 3 prime untranslated region of the APOA5 gene, this variant alters a regulatory sequence that controls how much apolipoprotein A-V is produced [2]. The change affects binding sites for microRNAs, which are small molecules that regulate gene expression by targeting messenger RNA [4]. Specifically, the minor G allele is associated with reduced expression of the protective apolipoprotein A-V protein [4]. This reduction in protein levels impairs the body's ability to efficiently clear fats from the bloodstream, leading to higher circulating triglycerides [3].

Key Insight: This variant sits in a regulatory region where it alters microRNA binding, directly influencing how efficiently the liver clears fat from the bloodstream.

Location: APOA5. Chromosome 11 · 11q23.3 · 116.8 Mb

Genotype Frequencies

Estimated prevalence by population

Global 0.8%; European 0.5%; African < 0.1%; East Asian 5.3%; South Asian 4.4%; Americas 1.3%; Ashkenazi 0.8%; Finnish 0.7%; Middle Eastern 1.1%; Amish 1.1%.

Estimated GG genotype frequency.

Global 12.8%; European 13.2%; African 3.1%; East Asian 35.5%; South Asian 33.1%; Americas 20.0%; Ashkenazi 16.4%; Finnish 15.2%; Middle Eastern 18.9%; Amish 18.5%.

Estimated GA genotype frequency.

Global 86.4%; European 86.3%; African 96.8%; East Asian 59.1%; South Asian 62.5%; Americas 78.8%; Ashkenazi 82.8%; Finnish 84.1%; Middle Eastern 80.0%; Amish 80.4%.

Estimated AA genotype frequency.

Associated Traits

Showing effects for G/G genotype

Cardiovascular & Metabolic

Lipids & Cholesterol

Triglycerides. Evidence: 8/10. Source: PMID 24387992. Increased.

HDL Cholesterol. Evidence: 10/10. Source: PMID 21386085. Lowered.

LDL Cholesterol. Evidence: 9/10. Source: PMID 29507422. Increased.

Heart Disease

Heart Disease. Evidence: 4/10. Source: PMID 35915156. Increased Risk.

Hypertension

Blood Pressure. Evidence: 6/10. Source: PMID 21386085. Increased.

Nutrition & Metabolism

Vitamin & Mineral Metabolism

Vitamin D Levels. Evidence: 8/10. Source: PMID 33462484. Lowered.

Showing effects for A/A genotype

Triglycerides. Evidence: 8/10. Source: PMID 24387992. Typical.

HDL Cholesterol. Evidence: 10/10. Source: PMID 21386085. Typical.

LDL Cholesterol. Evidence: 9/10. Source: PMID 29507422. Typical.

Heart Disease. Evidence: 4/10. Source: PMID 35915156. Typical Risk.

Blood Pressure. Evidence: 6/10. Source: PMID 21386085. Typical.

Vitamin D Levels. Evidence: 8/10. Source: PMID 33462484. Typical.

Showing effects for G/A genotype

Triglycerides. Evidence: 8/10. Source: PMID 24387992. Moderately Increased.

HDL Cholesterol. Evidence: 10/10. Source: PMID 21386085. Moderately Lowered.

LDL Cholesterol. Evidence: 9/10. Source: PMID 29507422. Moderately Increased.

Heart Disease. Evidence: 4/10. Source: PMID 35915156. Moderately Increased.

Blood Pressure. Evidence: 6/10. Source: PMID 21386085. Moderately Increased.

Vitamin D Levels. Evidence: 8/10. Source: PMID 33462484. Moderately Lowered.

What GG Genotype Means

What this genotype means for the people who carry it

Sample genotype: GG (Homozygous)

Having two copies of the G allele is strongly linked to elevated blood triglyceride levels [1]. This genetic profile is associated with a reduction in circulating apolipoprotein A-V, which slows down the clearance of fat particles after meals [2]. Consequently, individuals with this genotype often show higher levels of LDL cholesterol and lower levels of protective HDL cholesterol [3]. These lipid imbalances contribute to an increased risk of coronary artery disease [4]. Additionally, this genotype is associated with slightly higher blood pressure and lower vitamin D levels [5]. Managing cardiovascular health through regular lipid panels and lifestyle adjustments is particularly relevant for this group.

Elevated blood triglycerides; Lower HDL cholesterol; Increased risk of coronary artery disease.

What AA Genotype Means

Sample genotype: AA (Homozygous)

Possessing two copies of the common A allele is associated with typical, healthy levels of blood triglycerides [1]. This genotype ensures standard production of apolipoprotein A-V, allowing the body to efficiently clear fat particles from the bloodstream [2]. As a result, individuals with this profile generally maintain typical levels of protective HDL cholesterol and lower LDL cholesterol [3]. This balanced lipid profile is linked to a standard, baseline risk of coronary artery disease [4]. Furthermore, this genotype is associated with typical blood pressure and standard vitamin D levels [5]. Maintaining a balanced diet and regular exercise supports this favorable genetic baseline.

Typical blood triglyceride levels; Standard HDL and LDL cholesterol levels; Baseline risk of coronary artery disease.

What GA Genotype Means

Sample genotype: GA (Heterozygous)

Inheriting one copy of the G allele is associated with a moderate increase in blood triglyceride levels compared to the common genotype [1]. This change occurs because a single copy of the G allele reduces the overall production of apolipoprotein A-V in the liver [2]. The resulting slower clearance of dietary fats can lead to slightly higher total and LDL cholesterol levels [3]. Over time, these elevated lipid levels are associated with a modest increase in the risk of coronary artery disease [4]. This genotype is also linked to slightly lower levels of protective HDL cholesterol and vitamin D [5].

Moderately elevated triglycerides; Slightly lower HDL cholesterol; Modestly increased risk of coronary artery disease.

Related Variants

Variants with shared genetic architecture

rs3135506 · APOA5 Gene · Chr 11 · Triglyceride and Lipid Levels

rs651821 · APOA5 Gene · Chr 11 · Triglyceride Levels

rs662799 · APOA5 Gene · Chr 11 · Triglyceride Levels

Sources

Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.

An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.

An APOA5 3' UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site.

A large electronic-health-record-based genome-wide study of serum lipids.

Large-scale genome-wide association study of coronary artery disease in genetically diverse populations.

Genetics of 35 blood and urine biomarkers in the UK Biobank.

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Content updated August 2026.

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