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How CETP Genetics Affect Your Cholesterol and Heart Health

Cholesterol is a fat like substance the body needs for hormone production, vitamin D synthesis, and digestion. It travels in the blood inside lipoproteins. Low density lipoprotein or LDL is often called "bad" cholesterol because excess LDL can build up in arteries. High density lipoprotein or HDL is considered "good" cholesterol because it helps remove excess cholesterol from the bloodstream and arteries.

The CETP gene makes a protein called cholesteryl ester transfer protein. CETP moves fats and cholesteryl esters between HDL and LDL particles. Variations in CETP can change how active this protein is, which influences HDL and LDL levels and can affect cardiovascular risk. Below you will find an explanation of common CETP genotypes for the single variant rs3764261 and what they tend to mean for HDL, LDL, and heart attack risk.

Genetic Interpretations

2 effect alleles (AA) — Reduced CETP activity, higher HDL

If you have the AA genotype for rs3764261, you carry two copies of the effect allele. This variant is linked with reduced CETP activity, which means less transfer of cholesteryl esters from HDL to LDL. As a result, HDL levels tend to be higher. Higher HDL supports reverse cholesterol transport, the process by which HDL particles collect excess cholesterol from artery walls and deliver it to the liver for removal.

People with this genotype are often observed to have a lower risk of heart attack compared to those without the variant. Higher HDL can help limit plaque buildup that narrows arteries and leads to cardiovascular events. Even with a favorable CETP-related effect, maintaining heart healthy habits remains important.

1 effect allele (AC) — Moderately reduced CETP activity, likely higher HDL

If you have the AC genotype for rs3764261, you carry one copy of the effect allele. This genotype is associated with reduced but intermediate CETP activity. Less CETP activity generally means less cholesterol moves from HDL to LDL, which tends to leave HDL levels higher than average.

Higher HDL associated with this genotype supports reverse cholesterol transport and is linked with a lower risk of heart attack compared to the non-effect genotype. Lifestyle and other genetic factors will still influence your overall cholesterol profile and cardiovascular risk.

0 effect alleles (CC) — Typical CETP activity, typical HDL levels

If you have the CC genotype for rs3764261, you carry two copies of the non-effect allele. CETP activity in this case is expected to be typical. Your CETP protein performs the usual exchange of cholesteryl esters and triglycerides among lipoproteins, resulting in average HDL levels compared to people with reduced CETP activity.

With this genotype, your cholesterol balance and heart disease risk will be shaped primarily by lifestyle and other genetic factors. Diet, exercise, body weight, smoking status, and medical conditions like diabetes have strong effects on your cholesterol numbers and cardiovascular health.

What This Means for Your Health

Genetic differences in CETP can influence HDL levels, but they are only one part of the picture. Higher HDL linked to reduced CETP activity is generally beneficial for cardiovascular health, yet it does not guarantee protection. LDL levels, total cholesterol, triglycerides, blood pressure, blood sugar control, inflammation, and lifestyle factors all play major roles in heart disease risk.

PlexusDx does not provide medical advice. This information is educational and intended to help you understand genetic predispositions. Always consult your healthcare provider before making changes to your medications, supplements, or health plan.

Diet Recommendations

  • Follow a heart healthy dietary pattern rich in fruits, vegetables, whole grains, legumes, nuts, and seeds.
  • Choose healthy fats such as olive oil, avocado, and fatty fish. Limit saturated fats from red and processed meats and full fat dairy.
  • Include oily fish like salmon, mackerel, or sardines twice per week to boost omega-3 intake.
  • Increase soluble fiber from oats, barley, beans, apples, and citrus to help lower LDL.
  • Use plant sterol or stanol containing foods or spreads as part of a cholesterol lowering strategy, with guidance from your clinician.
  • Limit refined carbohydrates, sugary drinks, and trans fats found in many processed foods.

Supplement Recommendations

  • Omega-3 supplements (EPA and DHA) can lower triglycerides and support heart health. Discuss dose with your provider.
  • Plant sterol supplements may lower LDL by blocking cholesterol absorption. Use under medical supervision.
  • Niacin can raise HDL but has side effects and interacts with medications. Only consider under physician direction.
  • Fiber supplements such as psyllium can support LDL lowering when diet is inadequate.

Lifestyle Recommendations

  • Exercise most days of the week. Aim for at least 150 minutes of moderate activity or 75 minutes of vigorous activity per week, plus muscle strengthening twice weekly.
  • Achieve and maintain a healthy weight. Losing 5 to 10 percent of body weight can improve cholesterol and triglycerides.
  • Quit smoking. Smoking worsens lipid profiles and damages blood vessels.
  • Limit alcohol. Excess alcohol raises triglycerides and can harm heart health.
  • Manage stress through sleep, relaxation techniques, and regular physical activity.
  • Get routine health checks. Monitor blood pressure, blood sugar, and fasting lipid panels as recommended by your clinician.

Tests and Follow Up

  • Ask your healthcare provider about a fasting lipid panel to measure LDL, HDL, total cholesterol, and triglycerides.
  • Consider advanced lipid testing or inflammatory markers if you have personal or family history of early heart disease.
  • Discuss medication options if lifestyle changes are insufficient to reach target LDL or if you have high overall cardiovascular risk.

Putting It Together

Your CETP rs3764261 genotype can give insight into tendencies for HDL levels and a modest difference in cardiovascular risk. However, genetics are not destiny. Diet, exercise, weight, smoking status, blood pressure, and blood sugar control remain the most powerful levers to manage cholesterol and reduce heart disease risk. If your genotype is associated with higher HDL this is a favorable feature, but it must be combined with a healthy lifestyle and regular medical care to provide the best protection for your heart.

PlexusDx does not provide medical advice. This content is educational only. Talk with your healthcare provider or a qualified clinician before making any changes to medications, supplements, or your care plan.