APOE rs429358: What Your Genotype Means
The rs429358 variant is a single nucleotide polymorphism located within the APOE gene. When combined with the rs7412 variant, it helps define the APOE epsilon 4 haplotype, which is statistically associated with an increased risk of late-onset Alzheimer disease.
What each genotype means
Baseline risk profile
This genotype is associated with the APOE epsilon 3 allele, which is considered the most common and neutral isoform regarding Alzheimer's disease risk. Individuals with this genotype do not carry the epsilon 4 risk variant at this position, though overall risk is influenced by many other genetic and lifestyle factors.
This is the most common genotype globally, found in the majority of the population across most ancestries.
Increased risk potential
Carrying one C allele at this position means you possess one copy of the APOE epsilon 4 haplotype, which is statistically associated with an increased risk for late-onset Alzheimer's disease and cardiovascular conditions. This risk is dose-dependent, meaning it is generally lower than in individuals who carry two copies of the C allele.
Carried by a significant portion of the population, with frequencies varying by ancestry, typically ranging from 20% to 30% in many groups.
Elevated risk profile
Carrying two C alleles at this position indicates you possess two copies of the APOE epsilon 4 haplotype, which is the strongest known genetic risk factor for late-onset Alzheimer's disease. While this genotype is associated with higher statistical risk, it is not a clinical diagnosis, and many individuals with this profile do not develop the disease.
This genotype is the least common of the three, typically found in approximately 2% to 5% of many populations, though frequencies vary significantly by ancestry.
Understanding the rs429358 Variant
The rs429358 variant is a specific change in the DNA sequence located in the fourth exon of the APOE gene. In genetics, a single nucleotide polymorphism, or SNP, represents a variation at a single position in the DNA code. For rs429358, the two possible nucleotides at this position are thymine (T) and cytosine (C). This variant is particularly significant because it alters the amino acid sequence of the resulting apolipoprotein E protein. While the T allele is generally more common in many populations, the C allele is the key component that, when paired with specific variations at a nearby site called rs7412, forms the APOE epsilon 4 (ε4) haplotype. Because these two SNPs are inherited together, they are often analyzed as a pair to determine an individual's APOE status.
The Role of the APOE Gene
The APOE gene provides instructions for making a protein called apolipoprotein E. This protein is a major component of lipoproteins, which are particles that carry fats, including cholesterol, through the bloodstream. Apolipoprotein E is produced in several tissues, including the liver and the brain. In the central nervous system, it plays a critical role in lipid transport and the maintenance of neuronal health. Because of its involvement in cholesterol metabolism and its presence in amyloid plaques, researchers have studied the APOE gene extensively to understand its influence on brain function. Variations in this gene do not cause disease directly, but they are known to influence the efficiency of these biological processes, which may contribute to the development of certain health conditions over a lifetime.
Research and Health Associations
Extensive research has established a statistical association between the APOE ε4 haplotype and an increased risk of late-onset Alzheimer disease. The evidence for this association is strong and widely recognized in the scientific community. The risk is considered dose-dependent, meaning that individuals who inherit one copy of the ε4 haplotype generally have a different risk profile than those who inherit two copies. Beyond Alzheimer disease, the ε4 haplotype has also been studied for its potential links to cardiovascular health and other inflammatory conditions. It is important to note that possessing the ε4 haplotype does not mean an individual will develop Alzheimer disease, nor does its absence guarantee protection. Many other genetic and environmental factors contribute to the development of these complex conditions, and the predictive power of any single genetic variant is limited.
Population Frequency
The frequency of the C allele at rs429358 varies significantly across different global populations. Research indicates that the C allele frequency is approximately 10-15% in East Asian populations and 14-16% in European populations. In certain African populations, the frequency of this allele has been observed to be higher, sometimes exceeding 25%. These variations reflect the diverse genetic history of human populations. Because these frequencies differ, the prevalence of the associated ε4 haplotype is not uniform worldwide. Understanding these population-specific frequencies is a key area of study in human genetics, as it helps researchers contextualize how genetic risk factors are distributed across different ancestral groups.
Interpreting Your Genetic Information
Genetic information regarding the APOE gene is complex and should be interpreted with caution. Knowing your genotype for rs429358 provides insight into your genetic makeup, but it is not a diagnostic tool for Alzheimer disease or cardiovascular conditions. Because these diseases are multifactorial, involving a combination of genetics, lifestyle, and environment, a single SNP result cannot predict individual health outcomes. If you have concerns about your health or family history, the most appropriate step is to consult with a healthcare professional or a genetic counselor. They can help you understand the limitations of genetic testing and discuss how this information fits into your overall health picture. Never use genetic test results to make medical decisions or changes to your lifestyle without professional guidance.
How common is this variant?
The C allele frequency at rs429358 ranges from 10-15% in East Asians and 14-16% in Europeans, to over 25% in certain African populations.
Frequently asked questions
Does having the APOE epsilon 4 allele mean I will get Alzheimer's?
No, having the APOE epsilon 4 allele does not mean you will develop Alzheimer disease. It is considered a risk factor, meaning it increases the statistical likelihood, but it is not a deterministic cause.
Can I change my APOE genotype?
No, your genotype is determined at conception and cannot be changed. However, lifestyle factors such as diet, exercise, and cognitive engagement are studied for their potential role in supporting brain health regardless of genetic background.
Why are there two SNPs used to define APOE status?
The three common APOE alleles (epsilon 2, 3, and 4) are defined by the specific combination of variants at both the rs429358 and rs7412 positions. Looking at both SNPs is necessary to accurately identify which of the three major APOE forms an individual carries.
Should I get tested for APOE?
Genetic testing for APOE is a personal decision that should be discussed with a healthcare provider or genetic counselor. It is important to consider the psychological and medical implications of knowing your genetic risk for conditions that currently have limited preventative options.
Sources & further reading
Educational information only, last refreshed 9/26/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs429358?
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 APOE
Variant in the APOE/TOMM40 locus associated with late-onset Alzheimer's disease risk.
Downstream variant in the APOE region associated with lipid metabolism profiles and healthspan indicators.
Variant (c.497G>A, p.Arg166Gln) in the APOE gene known as Apolipoprotein E4 Christchurch, which has been shown in clinical case studies to confer resistance to familial Alzheimer's disease pathology.
Defines the APOE ε2 allele, associated with lower LDL cholesterol and reduced risk of Alzheimer's disease.
Upstream regulatory variant influencing APOE transcription and plasma lipid modulation.
Regulatory variant in the APOE promoter region modulating transcriptional activity and risk for late-onset neurodegeneration.