What you carry at this position in your DNA and what research says about it.
Heart and Lipid Health: 6/10 evidence, 12 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): C/C
Typical Cardiovascular Risk and Higher HDL Cholesterol
The common C/C genotype is associated with higher HDL cholesterol levels and a typical baseline risk for heart disease. It also indicates a standard response to certain calcium channel blocker medications.
What this genotype means: Typical baseline cardiovascular risk; Higher HDL cholesterol levels; Standard response to verapamil.
Sample genotype (not yours): C/T
Increased Cardiovascular Risk and Lower HDL Cholesterol
Presence of one T allele is associated with slightly lower HDL cholesterol and an increased risk of cardiovascular complications. This risk may be further elevated when taking the blood pressure medication verapamil.
What this genotype means: Slightly increased cardiovascular risk; Lower HDL cholesterol levels; Elevated risk of adverse events on verapamil.
Sample genotype (not yours): T/T
Higher Cardiovascular Risk and Lower HDL Cholesterol
The rare T/T genotype is associated with lower HDL cholesterol and a significantly higher risk of carotid artery disease and stroke. This risk is particularly elevated when using the blood pressure medication verapamil.
What this genotype means: Increased risk of carotid artery disease; Lower HDL cholesterol levels; Significantly elevated risk of adverse events on verapamil.
Gene function and biological role
Gene Function: NR1H3 encodes liver X receptor alpha (LXRα), a nuclear receptor that acts as a key sensor and regulator of cholesterol homeostasis and lipid metabolism. It controls the expression of genes involved in cholesterol efflux, transport, and excretion. LXRα activation generally promotes the clearance of excess cholesterol from peripheral tissues, protecting against plaque buildup in arteries. Variations in this gene can alter lipid profiles and influence susceptibility to cardiovascular diseases.
Variant Impact: The rs2279238 variant is a synonymous change (p.Ser99=) in the NR1H3 gene, meaning it does not alter the amino acid sequence of the LXRα protein. However, synonymous variants can still affect gene expression, mRNA stability, or translation efficiency. This genetic variation has been linked to differences in circulating lipid levels, including HDL cholesterol. It also modulates the risk of developing carotid artery disease and ischemic stroke. Furthermore, it influences how cardiovascular outcomes are affected by certain blood pressure medications.
Key Insight: The T allele of this variant is linked to a higher risk of stroke and carotid artery atherosclerosis, and it also increases the risk of adverse cardiovascular events specifically when taking the blood pressure medication verapamil.
Location: NR1H3. Chromosome 11 · 11p11.2 · 47.3 Mb
Estimated prevalence by population
Global 56.5%; European 71.1%; African 38.4%; East Asian 12.2%; South Asian 57.8%; Americas 53.0%; Ashkenazi 75.5%; Finnish 49.6%; Middle Eastern 73.5%; Amish 84.4%.
Estimated CC genotype frequency.
Global 35.4%; European 26.4%; African 47.2%; East Asian 45.5%; South Asian 36.4%; Americas 39.6%; Ashkenazi 22.8%; Finnish 41.7%; Middle Eastern 24.5%; Amish 14.9%.
Estimated CT genotype frequency.
Global 8.2%; European 2.5%; African 14.5%; East Asian 42.3%; South Asian 5.7%; Americas 7.4%; Ashkenazi 1.7%; Finnish 8.7%; Middle Eastern 2.0%; Amish 0.7%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Heart Disease
Cardiovascular Risk. Evidence: 5/10. Source: PMID 21562465. Typical Risk.
Lipids & Cholesterol
HDL Cholesterol. Evidence: 6/10. Source: PMID 35213538. Higher Levels.
Triglyceride to HDL Ratio. Evidence: 6/10. Source: PMID 35213538. Higher Ratio.
Stroke
Stroke. Evidence: 5/10. Source: PMID 21562465. Typical Risk.
Pharmacogenomics
Cardiovascular Drug Response
Verapamil Response. Evidence: 5/10. Source: PMID 21562465. Typical Response.
Showing effects for C/T genotype
Cardiovascular Risk. Evidence: 5/10. Source: PMID 21562465. Increased Risk.
HDL Cholesterol. Evidence: 6/10. Source: PMID 35213538. Intermediate Levels.
Triglyceride to HDL Ratio. Evidence: 6/10. Source: PMID 35213538. Intermediate Ratio.
Stroke. Evidence: 5/10. Source: PMID 21562465. Increased Risk.
Verapamil Response. Evidence: 5/10. Source: PMID 21562465. Increased Risk.
Showing effects for T/T genotype
HDL Cholesterol. Evidence: 6/10. Source: PMID 35213538. Lower Levels.
Triglyceride to HDL Ratio. Evidence: 6/10. Source: PMID 35213538. Lower Ratio.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
LXRα activation is generally favorable for cardiovascular health when the C/C genotype is present. This genotype is associated with higher levels of high-density lipoprotein (HDL) cholesterol, often referred to as good cholesterol, which helps clear excess lipids from the bloodstream [1]. Research indicates that individuals with the C/C genotype do not carry the elevated risk of carotid artery stenosis or ischemic stroke associated with the T allele [2]. Furthermore, clinical studies like the INVEST-GENES trial show that C/C carriers have a typical, lower risk of adverse cardiovascular events when treated with standard antihypertensive therapies [2]. This means that common blood pressure medications like verapamil do not carry the same elevated risk of heart attack or stroke seen in T allele carriers [2]. Maintaining a heart-healthy lifestyle remains beneficial for overall lipid management.
Typical baseline cardiovascular risk; Higher HDL cholesterol levels; Standard response to verapamil.
Sample genotype: CT (Heterozygous)
A single copy of the T allele is linked to a higher susceptibility to cardiovascular issues compared to the C/C genotype. This genetic profile is associated with lower levels of protective HDL cholesterol, which can influence overall lipid balance [1]. Clinical evidence from the INVEST-GENES study indicates that carriers of the T allele have an increased risk of adverse cardiovascular outcomes, such as heart attacks and strokes [2]. This risk is particularly pronounced in individuals treated with the calcium channel blocker verapamil, where the risk of adverse events was significantly higher compared to other treatment strategies [2]. Additionally, the T allele has been associated with a higher prevalence of carotid artery disease and ischemic stroke in various populations [2]. Discussing these findings with a healthcare provider can help tailor cardiovascular prevention and medication choices.
Slightly increased cardiovascular risk; Lower HDL cholesterol levels; Elevated risk of adverse events on verapamil.
Sample genotype: TT (Homozygous)
The T/T genotype carries the strongest association with adverse cardiovascular outcomes at this locus. This genotype is linked to lower levels of protective HDL cholesterol, which may impair the body's ability to clear arterial plaque [1]. Research has demonstrated a significant association between the T/T genotype and advanced carotid artery stenosis, a major risk factor for stroke [2]. Furthermore, the INVEST-GENES clinical trial revealed that T/T homozygotes have a substantially increased risk of heart attack and stroke, particularly when treated with the antihypertensive drug verapamil [2]. For these individuals, alternative blood pressure management strategies may offer a safer profile [2]. Proactive monitoring of lipid levels and cardiovascular health is highly recommended for those with this genetic profile.
Increased risk of carotid artery disease; Lower HDL cholesterol levels; Significantly elevated risk of adverse events on verapamil.
Variants with shared genetic architecture
rs10838681 · NR1H3 Gene · Chr 11 · Triglycerides and Lipids
rs7120118 · NR1H3 Gene · Chr 11 · Cholesterol and Brain Health
rs5065 · NPPA-AS1 Gene · Chr 1 · Heart and Stroke Risk
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