CDKN2B-AS1 rs1333049: What Your Genotype Means for Heart Health
The rs1333049 variant is a well-known genetic marker located in the CDKN2B-AS1 gene on chromosome 9. Extensive research has established a moderate statistical association between this single nucleotide polymorphism and an increased risk of coronary artery disease. While it is a common variant globally, it is just one of many genetic and lifestyle factors that influence overall cardiovascular health.
What each genotype means
Increased coronary artery risk
This genotype is associated with a higher statistical risk of developing coronary artery disease compared to those without the risk allele. Research indicates this variant at the 9p21 locus may influence disease susceptibility, though it does not guarantee the development of heart conditions. Please discuss your overall cardiovascular health and risk factors with your healthcare provider.
This genotype is common in many populations, with studies noting it is carried by approximately 22% of certain European-descent cohorts.
Elevated coronary artery risk
Carrying one copy of the risk allele is associated with a moderate increase in the statistical risk of coronary artery disease. This variant is a well-studied marker for heart health, but individual risk is influenced by a combination of genetics, lifestyle, and environment. Consult with your clinician to review your cardiovascular health profile.
This is a common genotype, observed in approximately 52% of participants in some studies of European ancestry.
Baseline coronary artery risk
This genotype does not carry the risk allele associated with increased susceptibility to coronary artery disease at this specific location. While this suggests a lower genetic risk relative to carriers of the C allele, it does not eliminate the possibility of heart disease. Maintaining a heart-healthy lifestyle remains important for everyone regardless of this genetic result.
This genotype is found at a significant frequency across global populations, representing the non-risk homozygous state.
What is rs1333049 and where is it located?
The rs1333049 variant is a single nucleotide polymorphism (SNP) situated on chromosome 9, specifically within the 9p21.3 genomic region. This area of the genome is widely recognized in cardiovascular genetics because it houses the CDKN2B-AS1 gene, which produces a long non-coding RNA (lncRNA) often referred to as ANRIL. Unlike genes that provide instructions for making proteins, long non-coding RNAs like the one produced by CDKN2B-AS1 help regulate how other genes are turned on or off. Research indicates that this specific lncRNA plays a critical role in managing cellular processes such as inflammation, cell proliferation, and cellular aging. Because these biological processes are deeply intertwined with the health of blood vessels, variations in this region can influence how the body responds to vascular stress. The rs1333049 variant represents a simple swap of one DNA building block for another—typically a change between the C and G alleles—which can subtly alter the regulatory functions of the CDKN2B-AS1 gene.
The link to coronary artery disease
Over the past decade, genome-wide association studies have consistently identified the 9p21.3 region as a hotspot for cardiovascular risk. The rs1333049 variant, in particular, is a well-established marker for coronary artery disease and myocardial infarction. Studies show that individuals carrying the risk allele, which is typically the C allele, have a statistically higher likelihood of developing coronary artery disease compared to those without it. Furthermore, research has linked this variant to an increased prevalence of peripheral artery disease and an earlier age of onset for coronary issues in certain populations. However, it is crucial to understand the strength of this evidence. While the statistical association is highly reproducible and considered moderate to strong in genomics research, the actual effect size of this single variant is relatively small. Carrying the risk allele does not guarantee that a person will develop heart disease, nor does lacking it confer absolute immunity. Instead, rs1333049 acts as one small piece of a much larger puzzle, interacting with other genetic variants and environmental factors.
Population frequency and global prevalence
The rs1333049 variant is remarkably common across global populations, which is typical for many genetic markers associated with complex, age-related conditions like coronary artery disease. Genomic databases indicate that the minor allele frequency hovers around forty-three percent globally. Because both the C and G alleles are so widespread, a large portion of the general population carries at least one copy of the risk-associated C allele. In fact, studies examining diverse groups frequently report that roughly half of the individuals tested are heterozygous, meaning they carry one C and one G allele. Meanwhile, about twenty to thirty percent of people may carry two copies of the risk allele, and a similar percentage carry two copies of the non-risk allele. This high prevalence underscores that rs1333049 is a normal, everyday variation in the human genome rather than a rare mutation. It highlights exactly why lifestyle and environmental factors remain critical in determining actual disease outcomes alongside our genetic predispositions.
What you can and cannot do with this information
Discovering your genotype for the rs1333049 variant can be an interesting window into your genetic predispositions, but it is important to interpret this information correctly. You cannot use this genetic marker to diagnose coronary artery disease, predict a heart attack, or determine your need for cardiovascular medications. Because the variant only exerts a modest influence on your overall risk, it should never replace standard medical evaluations like cholesterol tests, blood pressure monitoring, or clinical risk scoring. What you can do with this information is use it as a motivational tool to prioritize heart-healthy habits. Since the CDKN2B-AS1 gene interacts with inflammatory pathways and lipid metabolism, maintaining a balanced diet, engaging in regular physical activity, and avoiding smoking are highly effective ways to support your vascular health, regardless of your genetic makeup. If you have a family history of heart disease or are concerned about your cardiovascular risk, you should discuss these factors with a healthcare provider to understand your complete risk profile.
How common is this variant?
The rs1333049 variant is highly common globally, with the minor allele appearing in approximately 43% of the population. Because both alleles are widespread, it is entirely normal to carry one or two copies of the risk variant across all major ancestries.
Frequently asked questions
What is the CDKN2B-AS1 gene?
CDKN2B-AS1 is a gene located on chromosome 9 that produces a long non-coding RNA, often called ANRIL. Instead of making proteins, it helps regulate other genes involved in cell growth, inflammation, and aging.
Does having the risk allele mean I will get heart disease?
No, carrying the risk allele for rs1333049 does not guarantee you will develop heart disease. It is just one of many genetic and lifestyle factors that contribute to your overall cardiovascular risk.
Can I change my genetic risk for coronary artery disease?
While you cannot change your DNA, you can heavily influence your actual risk through lifestyle choices. A heart-healthy diet, regular exercise, and avoiding smoking can offset many genetic predispositions.
Why is the 9p21 chromosome region important?
The 9p21 genomic region is famous in genetics because it was one of the first areas consistently linked to heart disease in large genome-wide association studies. It contains several regulatory elements that affect vascular health.
Should I take medication based on my rs1333049 genotype?
No, you should never start, stop, or change medications based solely on a genetic test result for this variant. Always discuss your cardiovascular health and any medication needs with a qualified healthcare provider.
Sources & further reading
Educational information only, last refreshed 9/4/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs1333049?
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 CDKN2B-AS1
This variant in the CDKN2B-AS1 long noncoding RNA gene is associated with extreme longevity in genome-wide association studies.
A non-coding variant in the CDKN2B-AS1 locus associated with human longevity and survival beyond 90 years of age.
Non-coding RNA locus SNP associated with endometriosis development through altered regulation of cell cycle progression and local tissue remodeling.
This variant is a well-established risk locus for coronary artery disease and related cardiovascular conditions.
Located in the non-coding CDKN2B-AS1 locus, this variant confers significant risk for normal-tension and primary open-angle glaucoma.
Chromosome 9p21 non-coding regulatory variant conferring increased predisposition to coronary artery disease, myocardial infarction, and intracranial aneurysm.