What you carry at this position in your DNA and what research says about it.
Lifespan and Brain Health: 10/10 evidence, 39 publications.
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Sample genotype (not yours): G/G
Enhanced Longevity and Lower Dementia Risk
Two copies of the G allele are linked to higher levels of good HDL cholesterol. Favorable cardiovascular profiles and a lower risk of cognitive decline support healthy aging.
What this genotype means: Significantly higher HDL cholesterol levels; Up to 70% lower risk of Alzheimer's disease; Increased likelihood of exceptional longevity.
Sample genotype (not yours): A/A
Typical Lifespan and Cognitive Decline Risk
Two copies of the A allele represent the typical genetic baseline for cholesterol transport. Standard cardiovascular and cognitive aging patterns are expected without the unique protective effects of the G allele.
What this genotype means: Typical HDL and LDL cholesterol levels; Standard baseline risk for cognitive decline; Favorable response to simvastatin therapy.
Sample genotype (not yours): G/A
Moderate Longevity Benefit and Lower Dementia Risk
One copy of the G allele is associated with moderately higher good cholesterol. Healthy aging is supported by a helpful buffer against cognitive decline.
What this genotype means: Moderately higher HDL cholesterol levels; Reduced risk of dementia and Alzheimer's; Favorable response to statin therapy.
Gene function and biological role
Gene Function: The CETP gene encodes cholesteryl ester transfer protein, a key player in lipid metabolism [1]. This protein facilitates the exchange of cholesteryl esters and triglycerides between high-density lipoproteins (HDL) and other lipoprotein particles [1]. Lower activity of this protein is associated with higher levels of HDL, often called good cholesterol [2]. Because of its central role in managing blood lipids, CETP is a major focus of research into cardiovascular health, cognitive decline, and human longevity [2] [3].
Variant Impact: A missense mutation in the CETP gene changes the amino acid at position 422 (historically referred to as position 405) from isoleucine to valine [2]. This change, known as p.Val422Ile or I405V, directly alters the structure of the cholesteryl ester transfer protein [2]. The G allele encodes valine, which reduces the overall activity and concentration of the CETP protein in the bloodstream [1]. This reduction in activity leads to larger, more protective HDL and LDL particles, which are believed to support cardiovascular and brain health [1] [3].
Key Insight: People with two copies of the G allele have been shown to have up to a 70 percent lower risk of developing dementia and Alzheimer's disease.
Location: CETP. Chromosome 16 · 16q13 · 57.0 Mb
Estimated prevalence by population
Global 18.0%; European 10.1%; African 33.1%; East Asian 19.8%; South Asian 19.1%; Americas 13.9%; Ashkenazi 17.2%; Finnish 14.3%; Middle Eastern 16.7%; Amish 29.1%.
Estimated GG genotype frequency.
Global 46.0%; European 43.3%; African 48.9%; East Asian 49.4%; South Asian 49.2%; Americas 46.8%; Ashkenazi 48.5%; Finnish 47.0%; Middle Eastern 48.3%; Amish 49.7%.
Estimated GA genotype frequency.
Global 35.9%; European 46.6%; African 18.0%; East Asian 30.9%; South Asian 31.7%; Americas 39.3%; Ashkenazi 34.3%; Finnish 38.6%; Middle Eastern 35.0%; Amish 21.2%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Lifestyle, Fitness & Aging
Aging & Longevity
Lifespan. Evidence: 3/10. Source: PMID 14559957. Longer Lifespan.
Neurology & Mental Health
Neurodegenerative Diseases
Dementia. Evidence: 3/10. Source: PMID 20068209. ~70% Lower Risk.
Cardiovascular & Metabolic
Lipids & Cholesterol
HDL Cholesterol. Evidence: 10/10. Source: PMID 33462484. Higher Levels.
LDL Cholesterol. Evidence: 8/10. Source: PMID 33462484. Lower Levels.
Showing effects for A/A genotype
Lifespan. Evidence: 3/10. Source: PMID 14559957. Typical Lifespan.
Dementia. Evidence: 3/10. Source: PMID 20068209. Typical Risk.
HDL Cholesterol. Evidence: 10/10. Source: PMID 33462484. Typical Levels.
LDL Cholesterol. Evidence: 8/10. Source: PMID 33462484. Typical Levels.
Showing effects for G/A genotype
Lifespan. Evidence: 3/10. Source: PMID 14559957. Slightly Longer.
Dementia. Evidence: 3/10. Source: PMID 20068209. Lower Risk.
HDL Cholesterol. Evidence: 10/10. Source: PMID 33462484. Slightly Higher.
LDL Cholesterol. Evidence: 8/10. Source: PMID 33462484. Slightly Lower.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Inheriting two copies of the G allele is associated with a lower concentration and reduced activity of the CETP protein [1]. This reduction leads to larger lipoprotein particles and significantly higher levels of HDL cholesterol [1]. Clinical studies have shown that individuals with this genotype are more likely to achieve exceptional longevity [1] [2]. Furthermore, research indicates that G/G homozygotes have an average of 70% lower risk of developing dementia and Alzheimer's disease [3]. This protective effect is thought to stem from the preservation of cognitive function and healthier blood vessels in the brain [2] [3]. Additionally, individuals with this genotype may show an enhanced response to rosuvastatin therapy [4].
Significantly higher HDL cholesterol levels; Up to 70% lower risk of Alzheimer's disease; Increased likelihood of exceptional longevity.
Sample genotype: AA (Homozygous)
Inheriting two copies of the A allele results in typical levels of CETP protein activity [1]. This standard activity level is associated with typical particle sizes for both HDL and LDL cholesterol [1]. Unlike carriers of the G allele, individuals with the A/A genotype do not experience the genetic reduction in dementia or Alzheimer's risk [2]. However, this genotype represents the most common pattern globally and does not inherently cause disease [3]. While it lacks the exceptional longevity association, standard cardiovascular prevention strategies remain highly effective [1] [3]. Interestingly, individuals with this genotype may experience a better response to simvastatin therapy compared to other genotypes [4].
Typical HDL and LDL cholesterol levels; Standard baseline risk for cognitive decline; Favorable response to simvastatin therapy.
Sample genotype: GA (Heterozygous)
A single copy of the G allele results in a moderate reduction in CETP activity [1]. This intermediate level of activity leads to moderately higher HDL cholesterol levels compared to the typical baseline [1]. Studies suggest that individuals with the G/A genotype enjoy a lower risk of dementia and Alzheimer's disease [2]. While the longevity benefit is less pronounced than in G/G homozygotes, it still represents a favorable pattern for healthy aging [1] [3]. People with this genotype also tend to respond well to lipid-lowering therapies like rosuvastatin [4].
Moderately higher HDL cholesterol levels; Reduced risk of dementia and Alzheimer's; Favorable response to statin therapy.
Variants with shared genetic architecture
rs12720922 · CETP Gene · Chr 16 · Cholesterol and Heart Health
rs1532624 · CETP Gene · Chr 16 · Lipid Levels and Statins
rs17231506 · CETP Gene · Chr 16 · Cardiovascular Health
Unique lipoprotein phenotype and genotype associated with exceptional longevity.
A genotype of exceptional longevity is associated with preservation of cognitive function.
Genetic contribution to lipid target achievement with statin therapy: a prospective study.
Content updated August 2026.
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