What you carry at this position in your DNA and what research says about it.
LDL Cholesterol Levels: 10/10 evidence, 26 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): T/T
Lower LDL Cholesterol and Heart Disease Risk
Naturally lower levels of LDL cholesterol help protect against cardiovascular disease. However, this natural enzyme inhibition is linked to a very slight increase in type 2 diabetes risk and body weight.
What this genotype means: Naturally lower LDL cholesterol levels; Reduced risk of coronary artery disease; Slightly higher risk of type 2 diabetes.
Sample genotype (not yours): C/C
Higher LDL Cholesterol and Heart Disease Risk
Naturally higher levels of LDL cholesterol increase the risk of cardiovascular disease. This genetic profile is also associated with a lower response to moderate-intensity statin therapy.
What this genotype means: Elevated LDL and total cholesterol levels; Increased risk of coronary artery disease; Lower response to standard statin therapy.
Sample genotype (not yours): T/C
Typical LDL Cholesterol and Heart Disease Risk
A balanced genetic profile provides typical levels of LDL cholesterol and average cardiovascular risk. The metabolic trade-offs associated with enzyme inhibition are minimal with one copy of each allele.
What this genotype means: Typical circulating LDL cholesterol levels; Average risk of coronary artery disease; Standard response to statin medications.
Gene function and biological role
Gene Function: The HMGCR gene encodes 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis [1]. This enzyme is the primary cellular target of statins, which are widely prescribed to lower blood cholesterol levels [2]. By inhibiting HMGCR, these medications reduce the liver's production of cholesterol and increase its ability to clear low-density lipoprotein (LDL) from the blood [1]. Genetic variations in this gene can naturally alter enzyme activity, mimicking some of the biological effects of statin therapy [2].
Variant Impact: The rs12916 variant is located in the 3' untranslated region of the HMGCR gene, where it influences gene expression levels rather than altering the protein structure directly [3]. The T allele is associated with lower expression of the HMGCR enzyme, leading to naturally lower circulating levels of LDL cholesterol [1]. Conversely, the C allele is linked to higher expression, resulting in elevated cholesterol levels and a higher risk of cardiovascular events [4]. Because the T allele naturally reduces HMGCR activity, it also carries a slightly increased risk of type 2 diabetes and modest weight gain, mirroring the known metabolic side effects of statin medications [2].
Key Insight: The same genetic variant that lowers your cholesterol can slightly increase your risk of type 2 diabetes, mimicking the side effects of statin medications.
Location: HMGCR. Chromosome 5 · 5q13.3 · 75.4 Mb
Estimated prevalence by population
Global 40.0%; European 35.4%; African 56.8%; East Asian 21.8%; South Asian 20.2%; Americas 36.7%; Ashkenazi 28.3%; Finnish 30.1%; Middle Eastern 45.4%; Amish 37.7%.
Estimated TT genotype frequency.
Global 45.3%; European 48.2%; African 37.2%; East Asian 49.8%; South Asian 49.5%; Americas 47.8%; Ashkenazi 49.8%; Finnish 49.5%; Middle Eastern 44.0%; Amish 47.4%.
Estimated TC genotype frequency.
Global 14.7%; European 16.4%; African 6.1%; East Asian 28.4%; South Asian 30.3%; Americas 15.5%; Ashkenazi 21.9%; Finnish 20.4%; Middle Eastern 10.7%; Amish 14.9%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 10/10. Source: PMID 20686565. Lower LDL.
Heart Disease
Coronary Artery Disease. Evidence: 8/10. Source: PMID 36474045. Lower Risk.
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 3/10. Source: PMID 33167740. Slightly Higher Risk.
Obesity & Body Composition
Body Weight. Evidence: 3/10. Source: PMID 25262344. Slightly Higher.
Pharmacogenomics
Lipid-Lowering Drug Response
Statin Response. Evidence: 4/10. Source: PMID 33167740. Typical Response.
Showing effects for C/C genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 20686565. Higher LDL.
Coronary Artery Disease. Evidence: 8/10. Source: PMID 36474045. Elevated Risk.
Type 2 Diabetes. Evidence: 3/10. Source: PMID 33167740. Slightly Lower Risk.
Body Weight. Evidence: 3/10. Source: PMID 25262344. Slightly Lower.
Statin Response. Evidence: 4/10. Source: PMID 33167740. Lower Response.
Showing effects for T/C genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 20686565. Typical LDL.
Coronary Artery Disease. Evidence: 8/10. Source: PMID 36474045. Typical Risk.
Type 2 Diabetes. Evidence: 3/10. Source: PMID 33167740. Typical Risk.
Body Weight. Evidence: 3/10. Source: PMID 25262344. Typical.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Inheriting two copies of the T allele results in naturally reduced activity of the HMG-CoA reductase enzyme [1]. This natural reduction mimics the primary mechanism of statin drugs, leading to significantly lower circulating levels of LDL and total cholesterol [2]. Consequently, this genetic profile is associated with a reduced risk of developing coronary artery disease [3]. However, long-term genetic inhibition of this pathway also carries the same metabolic trade-offs seen with pharmacological statin use [4]. Studies show a modest increase in the risk of developing type 2 diabetes, along with small increases in body weight and waist circumference [4]. Despite these metabolic trade-offs, the cardiovascular benefits of lower LDL cholesterol generally outweigh the slight increase in diabetes risk [3]. Individuals with this genotype typically show a favorable lipid-lowering response when prescribed statin therapy [5].
Naturally lower LDL cholesterol levels; Reduced risk of coronary artery disease; Slightly higher risk of type 2 diabetes.
Sample genotype: CC (Homozygous)
Inheriting two copies of the C allele leads to higher expression of the HMGCR enzyme and elevated cholesterol production [1]. This results in significantly higher circulating levels of LDL cholesterol, total cholesterol, and apolipoprotein B [2]. Over time, these elevated lipid levels contribute to an increased risk of coronary artery disease [3]. On the positive side, the absence of natural HMGCR inhibition protects against the metabolic side effects associated with statins [4]. This genotype is linked to a slightly lower risk of type 2 diabetes and a lower average body weight [4]. However, when cardiovascular risk requires medical intervention, individuals with this profile may experience a reduced response to standard statin therapy [5]. They are more likely to have residual cholesterol risk and may respond less strongly to standard statin therapy, so target LDL levels can be harder to reach [5].
Elevated LDL and total cholesterol levels; Increased risk of coronary artery disease; Lower response to standard statin therapy.
Sample genotype: TC (Heterozygous)
Carrying one copy of each allele results in intermediate HMGCR enzyme activity and typical circulating lipid levels [1]. LDL cholesterol, total cholesterol, and apolipoprotein B levels generally fall within the average range for the population [2]. The risk of coronary artery disease is not significantly elevated or reduced compared to the general population [3]. Similarly, the minor metabolic side effects associated with HMGCR inhibition, such as increased diabetes risk or weight gain, are negligible [4]. This heterozygous profile represents a balanced baseline for cardiovascular and metabolic health. If lipid-lowering therapy becomes necessary, individuals with this genotype typically respond normally to standard statin doses [5]. Maintaining a heart-healthy diet and regular physical activity remains the most effective way to manage cardiovascular risk.
Typical circulating LDL cholesterol levels; Average risk of coronary artery disease; Standard response to statin medications.
Variants with shared genetic architecture
rs12654264 · HMGCR Gene · Chr 5 · Cholesterol and Statin Response
rs3846662 · HMGCR Gene · Chr 5 · Cholesterol and Statin Response
rs3846663 · HMGCR Gene · Chr 5 · Cholesterol Levels
Genome-wide characterization of circulating metabolic biomarkers.
Discovery and refinement of loci associated with lipid levels.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com