CETP rs11554805: What Your Genotype Means
The genetic variant rs11554805 (often historically evaluated alongside the I405V polymorphism) is located in the CETP gene on chromosome 16. It encodes a missense alteration, p.Ile422Val, that has been linked to reduced cholesteryl ester transfer protein activity and higher circulating levels of high-density lipoprotein cholesterol (HDL-C). However, the downstream protective effects against coronary artery disease remain modest and subject to ongoing scientific debate.
What each genotype means
Typical CETP activity
This genotype represents the more common version of the CETP gene in many populations, often referred to as the isoleucine (I) form at position 405. Research suggests this version is associated with standard levels of cholesteryl ester transfer protein activity compared to the valine (V) variant. It is considered the baseline for comparison in studies examining lipid metabolism and cardiovascular risk.
Carried by approximately 30% to 50% of individuals in many European and Asian populations.
Intermediate CETP activity
Carrying one copy of each allele means you have a mix of the isoleucine and valine forms of the CETP protein. Studies indicate that individuals with this genotype often show lipid profiles that fall between those of the AA and GG groups, typically with slightly higher HDL-cholesterol levels than those with the AA genotype. This is a common genetic variation and is not considered a medical condition.
This is the most common genotype, found in roughly 40% to 50% of individuals across many global populations.
Reduced CETP activity
This genotype corresponds to the valine (V) variant at position 405, which is associated with reduced activity of the cholesteryl ester transfer protein. Research consistently links this genotype to higher levels of HDL-cholesterol, which may provide a modest protective effect against coronary artery disease in some populations. Because lipid levels are influenced by many factors, you should discuss your overall cardiovascular health and lipid profile with your clinician.
Carried by roughly 10% to 25% of individuals, with frequencies varying significantly by ancestry.
Genomic Location and Variant Characteristics
The single nucleotide polymorphism rs11554805 resides within the cholesteryl ester transfer protein (CETP) gene on chromosome 16. In standard protein coding sequences, this missense variant is annotated as p.Ile422Val (or p.Ile405Val in legacy nomenclature reflecting the mature protein cleavage state). At the DNA level, the substitution alters the codon sequence to replace the amino acid isoleucine with valine. This subtle structural alteration influences how the CETP protein folds and operates in the bloodstream. Because it sits directly within an exon of the protein-coding sequence, geneticists classify it as a coding missense change. Rather than causing a total breakdown of the protein, the alteration slightly dampens the rate at which CETP carries out lipid transfers, creating a measurable biochemical shift in circulating lipoprotein particles.
The Biological Role of the CETP Gene
The CETP gene provides the instructions for producing cholesteryl ester transfer protein, a key plasma glycoprotein predominantly synthesized in the liver. CETP acts as a critical molecular shuttle in reverse cholesterol transport, transferring neutral lipids between circulating lipoproteins. Specifically, it facilitates the exchange of cholesteryl esters from high-density lipoproteins (HDL)—often referred to as 'good cholesterol'—to apolipoprotein B-containing lipoproteins, including low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL), in exchange for triglycerides. When CETP activity is reduced by genetic variation or pharmacological inhibition, fewer cholesteryl esters are transferred out of HDL particles. Consequently, circulating HDL-C levels rise, while LDL and VLDL lipid fractions may decline or remodel.
Scientific Evidence and Cardiovascular Health Associations
Multiple observational and candidate gene investigations have associated the valine-encoding allele of this polymorphism with increased plasma HDL-C concentrations and lower plasma CETP mass. Historically, researchers hypothesized that genetically driven increases in HDL-C would directly confer substantial cardiovascular protection. However, epidemiological studies across different cohorts have revealed a more complex picture. While some large meta-analyses report modest, weak inverse associations between reduced-function CETP variants and coronary artery disease (CAD), other investigations—including studies in diabetic cohorts and clinical trials targeting CETP—demonstrate that simply raising HDL-C does not automatically eliminate cardiovascular events. Because modern mendelian randomization studies show that the protective cardiovascular impact of CETP alterations may be driven primarily by concomitant reductions in atherogenic apoB particles rather than HDL-C elevation itself, the clinical evidence for direct cardioprotection from this single variant is categorized as limited and mixed.
Ancestry and Population Frequency Patterns
Unlike rare pathogenic mutations that cause complete CETP deficiency, the rs11554805 variant is common across world populations. The minor allele displays an estimated frequency ranging from roughly 0.30 to 0.45 in diverse ancestral groups, including European and East Asian populations. Genetic surveys have also detected notable frequency variations across South Asian, Middle Eastern, and African American populations. Because this polymorphism is widely distributed globally, possessing one or two copies of the variant allele is a typical human genetic variation rather than an anomalous or rare biological defect. Reference databases such as gnomAD and dbSNP highlight that a substantial proportion of the global population naturally carries the heterozygous or homozygous alternative genotype.
Clinical Utility and Lifestyle Considerations
Understanding your rs11554805 genotype offers educational insight into personal lipid biology, but it cannot be used as an independent clinical diagnosis. A genetic predisposition toward higher HDL-C does not grant immunity from atherosclerosis, nor does carrying the common isoleucine allele mean you will develop heart disease. Standard laboratory lipid panels (measuring total cholesterol, LDL-C, HDL-C, and triglycerides) alongside clinical evaluations remain the established standard for assessing cardiovascular risk. Furthermore, individuals considering lipid-lowering therapies or other cardiovascular medications should never alter their treatment regimen based solely on commercial genetic tests. Medical and lifestyle decisions should always be directed by a licensed physician or cardiologist in conjunction with comprehensive clinical biomarkers.
How common is this variant?
The minor valine-encoding allele occurs at a frequency of approximately 0.30 to 0.45 across European and Asian populations, making heterozygous and homozygous carriers widespread globally.
Frequently asked questions
Does having the CETP rs11554805 variant mean I won't get heart disease?
No. While the variant is statistically associated with higher HDL cholesterol levels and modest protection in some studies, cardiovascular health is multifactorial. Factors such as LDL cholesterol, blood pressure, smoking, diet, and lifestyle play far larger roles in overall heart disease risk.
What is the difference between p.Ile422Val and I405V?
They refer to the exact same amino acid change in the CETP protein. 'I405V' is legacy nomenclature based on the mature, processed CETP protein after its signal peptide is cleaved, whereas 'p.Ile422Val' reflects the standard full-length protein sequence under modern HGVS nomenclature.
Can I use this genetic result to adjust my cholesterol medications?
No, you should never start, stop, or change the dose of any cholesterol-lowering medication based on genetic testing results alone. Medication decisions must always be made in consultation with your doctor or pharmacist using actual blood lipid measurements.
Why is the evidence linking this variant to heart health considered limited?
Although the variant consistently correlates with slightly higher HDL cholesterol, clinical trials and large genetic studies have demonstrated that higher HDL cholesterol does not always translate into fewer heart attacks. The biological relationship between CETP activity, lipid remodeling, and vascular health is nuanced and varies across cohorts.
Sources & further reading
Educational information only, last refreshed 9/5/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs11554805?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in CETP
CETP promoter variant associated with preserved cognitive function, elevated HDL levels, and exceptional longevity across European cohorts.
The B2 (A) allele of the TaqIB polymorphism is associated with lower CETP activity and significantly higher HDL-cholesterol levels.
The I405V variant in CETP is associated with altered HDL cholesterol levels and cardiovascular risk profiles.
Well-established regulatory intronic polymorphism modulating cholesteryl ester transfer protein activity and circulating HDL cholesterol levels.
Known as the CETP TaqIB polymorphism, this intron variant is linked to reduced CETP activity, higher circulating HDL-C, and altered cardiovascular risk profile.
The I405V coding variant in cholesteryl ester transfer protein correlates with diminished CETP mass, elevated HDL cholesterol levels, and potential longevity benefits.