What you carry at this position in your DNA and what research says about it.
Cardiometabolic Health Risk: 10/10 evidence, 30 publications.
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Sample genotype (not yours): G/G
Typical Cardiometabolic Risk
A G/G genetic profile is associated with typical cardiovascular and metabolic health. It carries the protective G allele, which is linked to higher HDL cholesterol and lower triglycerides.
What this genotype means: Typical risk of coronary artery disease; Higher levels of protective HDL cholesterol; Typical waist-to-hip ratio.
Sample genotype (not yours): A/A
Elevated Cardiometabolic Risk
An A/A genetic profile is associated with an increased risk of coronary artery disease, higher triglycerides, and elevated blood pressure. It is also linked to a higher waist-to-hip ratio.
What this genotype means: Increased risk of coronary artery disease; Higher triglyceride levels; Increased waist-to-hip ratio.
Sample genotype (not yours): G/A
Slightly Elevated Cardiometabolic Risk
A G/A genetic profile is associated with a minor increase in the risk of coronary artery disease and type 2 diabetes. It may also lead to slightly higher triglyceride levels.
What this genotype means: Slightly increased risk of coronary artery disease; Slightly higher triglyceride levels; Marginally higher waist-to-hip ratio.
Gene function and biological role
Gene Function: The POLR1C gene encodes a subunit of RNA polymerases I and III, which are essential enzymes responsible for synthesizing ribosomal and transfer RNAs. This gene plays a fundamental role in cellular growth, protein synthesis, and basic metabolic maintenance. While POLR1C is critical for basic cellular functions, genomic variations in this region are also in close proximity to and in strong linkage disequilibrium with the VEGFA gene, which regulates blood vessel growth [1]. Consequently, genetic variants in this locus are frequently associated with systemic metabolic and cardiovascular traits. Researchers study this gene to understand how basic cellular machinery and vascular growth factors interact to influence metabolic health.
Variant Impact: The rs6905288 variant is an intronic change located within the POLR1C gene, but it is highly linked to the nearby VEGFA gene locus. This genetic variation is strongly associated with a cluster of cardiometabolic traits, including body fat distribution, blood lipid levels, and cardiovascular disease risk [2]. The A allele of this variant is linked to higher triglycerides, increased waist-to-hip ratio, and elevated risk of coronary artery disease [3]. Conversely, the G allele is associated with higher levels of protective HDL cholesterol. This variant serves as an important genetic marker for assessing inherited predispositions to metabolic syndrome and heart health.
Key Insight: This variant is located in the POLR1C gene but exerts its metabolic effects by influencing the expression of the nearby VEGFA gene in subcutaneous fat tissue.
Location: POLR1C. Chromosome 6 · 6p21.1 · 43.8 Mb
Estimated prevalence by population
Global 19.3%; European 18.8%; African 25.7%; East Asian 7.7%; South Asian 3.3%; Americas 16.1%; Ashkenazi 13.9%; Finnish 17.3%; Middle Eastern 10.7%; Amish 11.9%.
Estimated GG genotype frequency.
Global 48.2%; European 49.1%; African 50.0%; East Asian 40.1%; South Asian 29.8%; Americas 48.1%; Ashkenazi 46.8%; Finnish 48.6%; Middle Eastern 44.0%; Amish 45.2%.
Estimated GA genotype frequency.
Global 32.6%; European 32.1%; African 24.3%; East Asian 52.2%; South Asian 66.9%; Americas 35.8%; Ashkenazi 39.3%; Finnish 34.2%; Middle Eastern 45.4%; Amish 42.9%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cardiovascular & Metabolic
Heart Disease
Coronary Artery Disease. Evidence: 8/10. Source: PMID 22319020. Typical Risk.
Lipids & Cholesterol
HDL Cholesterol. Evidence: 10/10. Source: PMID 28334899. Higher Levels.
Triglycerides. Evidence: 8/10. Source: PMID 28334899. Typical Levels.
Obesity & Body Composition
Waist-to-Hip Ratio. Evidence: 10/10. Source: PMID 20935629. Typical Ratio.
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 8/10. Source: PMID 35551307. Typical Risk.
Hypertension
Blood Pressure. Evidence: 8/10. Source: PMID 38689001. Typical Pressure.
Showing effects for A/A genotype
Coronary Artery Disease. Evidence: 8/10. Source: PMID 22319020. Increased Risk.
HDL Cholesterol. Evidence: 10/10. Source: PMID 28334899. Lower Levels.
Triglycerides. Evidence: 8/10. Source: PMID 28334899. Higher Levels.
Waist-to-Hip Ratio. Evidence: 10/10. Source: PMID 20935629. Higher Ratio.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 35551307. Increased Risk.
Blood Pressure. Evidence: 8/10. Source: PMID 38689001. Higher Pressure.
Showing effects for G/A genotype
Coronary Artery Disease. Evidence: 8/10. Source: PMID 22319020. Slightly Increased.
HDL Cholesterol. Evidence: 10/10. Source: PMID 28334899. Typical Levels.
Triglycerides. Evidence: 8/10. Source: PMID 28334899. Slightly Higher.
Waist-to-Hip Ratio. Evidence: 10/10. Source: PMID 20935629. Slightly Higher.
Type 2 Diabetes. Evidence: 8/10. Source: PMID 35551307. Slightly Increased.
Blood Pressure. Evidence: 8/10. Source: PMID 38689001. Slightly Higher.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
A G/G genotype is generally favorable for cardiovascular and metabolic health. Large-scale genome-wide association studies show that carriers of this genotype do not inherit the risk-increasing A allele for coronary artery disease [1]. Furthermore, the G allele is robustly associated with higher levels of high-density lipoprotein (HDL) cholesterol, which is often referred to as the good cholesterol [2]. This genetic profile is also linked to typical triglyceride levels and a lower waist-to-hip ratio compared to carriers of the A allele [3]. These genetic factors collectively contribute to a more favorable metabolic profile and lower baseline risk for type 2 diabetes [4]. Blood pressure measurements also tend to remain in the typical range for individuals with this profile. Maintaining a balanced diet and regular exercise can help maximize these natural genetic advantages.
Typical risk of coronary artery disease; Higher levels of protective HDL cholesterol; Typical waist-to-hip ratio.
Sample genotype: AA (Homozygous)
An A/A genotype is associated with the highest genetic risk at this locus for several metabolic and cardiovascular conditions. Multiple large-scale genomic studies have linked this genotype to an increased risk of coronary artery disease [1]. This genetic profile is also associated with higher circulating triglycerides and lower levels of protective HDL cholesterol [2]. Additionally, individuals with the A/A genotype tend to have a higher waist-to-hip ratio, reflecting a predisposition to abdominal fat distribution [3]. These combined lipid and fat distribution patterns contribute to a higher risk of developing type 2 diabetes [4]. Blood pressure readings, both systolic and diastolic, are also frequently higher in individuals carrying two copies of the A allele. Proactive lifestyle management, including regular cardiovascular exercise and lipid monitoring, is particularly beneficial for individuals with this genetic profile.
Increased risk of coronary artery disease; Higher triglyceride levels; Increased waist-to-hip ratio; Elevated risk of type 2 diabetes.
Sample genotype: GA (Heterozygous)
A G/A genotype represents an intermediate genetic profile, carrying one copy of the risk-associated A allele and one copy of the protective G allele. This intermediate status is linked to a slightly elevated risk of developing coronary artery disease compared to the G/G genotype [1]. Metabolic studies indicate that carriers of the A allele tend to have slightly higher triglyceride levels and a marginally increased waist-to-hip ratio [2]. There is also a small, incremental increase in the likelihood of developing type 2 diabetes [3]. On the positive side, the presence of one G allele still provides some support for maintaining typical HDL cholesterol levels [4]. Blood pressure levels may also show a very slight upward trend compared to the G/G baseline. Focus on cardiovascular fitness and a low-glycemic diet can help mitigate these slight genetic risks.
Slightly increased risk of coronary artery disease; Slightly higher triglyceride levels; Marginally higher waist-to-hip ratio.
Variants with shared genetic architecture
rs1358980 · POLR1C Gene · Chr 6 · Body Fat Distribution
rs6921438 · POLR1C Gene · Chr 6 · Heart Disease Risk
rs998584 · POLR1C Gene · Chr 6 · Metabolic Health
Content updated August 2026.
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