The risk allele (oriented to the dbSNP entry) is most likely (C); the odds ratio associated with heterozygotes is 1.47 (CI 1.27-1.70), and for homozygotes, 1.9 (CI 1.61-2.24). [PMID 17554300]
This SNP has also been reported to have the highest association of any SNP studied in a subsequent experiment conducted with the resources of the German MI [Myocardial Infarction] Family Study. [PMID 17634449, PMID 18362232]
The initial studies were conducted on Caucasian populations. A subsequent study of Japanese and Korean patients has also found rs1333049 to be associated with increased coronary artery disease risk, with roughly similar odds ratios.[PMID 18264662]
[PMID 18652946] A long-term study of a cohort of 769 individuals finds that the rs1333049(C) allele was associated with:
- prevalent carotid atherosclerosis (odds ratio 1.46, 1.43 or 1.44, from data collected in 1990, 1995, and 2000, respectively, all with CI: ~1.1-1.9);
- progression of atherosclerosis (for example, odds ratio 1.87 (CI: 1.44 to 2.42) during 1995 to 2000);
- incident cardiovascular disease (hazard ratio: 1.37 (CI: 1.05 to 1.79)}.
- Note: this SNP and rs10757278 are practically equivalent, with linkage r2=1 in HapMap CEU populations
[PMID 19171343] In a cross-sectional study of individuals with stable coronary artery disease, there was no association with cardiovascular structure and function.
[PMID 20231156] A study of 3,000+ patients with acute coronary sydrome (ACS) revealed that those carrying a rs1333049(C) allele were at higher risk for subsequent myocardial infarctions [adjusted hazard ratio 1.48, CI: 1.00-2.19, p = 0.048 and with recurrent MI or cardiac death (adjusted HR 1.58, CI: 1.00-2.48, p = 0.045) within 6 months after an index ACS.
[PMID 19164808] Large scale association analysis of novel genetic loci for coronary artery disease
[PMID 19548844] Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese
[PMID 19709660] Single nucleotide polymorphism on chromosome 9p21 and endothelial progenitor cells in a general population cohort
[PMID 18675980] Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes
[PMID 19955471] Genetic Variants Identified in a European Genome-Wide Association Study That Were Found to Predict Incident Coronary Heart Disease in the Atherosclerosis Risk in Communities Study
[PMID 20031606] A study of 2630 white individuals (mean age, 76.4 years) concluded that the rs1333049(C) allele was associated with increased prevalence of peripheral artery disease. The per allele odds ratio was 1.29 (CI: 1.06 to 1.56, p = 0.012).
[PMID 20031580] Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study
[PMID 19926059] No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents
[PMID 20230275] Preliminary evidence of a genetic association between chromosome 9p21.3 and human longevity
[PMID 20427016] Single nucleotide polymorphism rs1333049 on chromosome 9p21.3 is associated with Alzheimer's disease in Han Chinese
[PMID 20649639] Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G>C polymorphism
[PMID 20691078] Chromosome 9p21.3 polymorphism in a Chinese Han population is associated with angiographic coronary plaque progression in non-diabetic but not in type 2 diabetic patients
[PMID 21152093] Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis
[PMID 21511257] The chromosome 9p21 region and myocardial infarction in a European population
|Title||A Genome-wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease.|
|Odds Ratio||1.2700 [1.23-1.31]|
[PMID 21385355] Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry
[PMID 22144573] Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction
[PMID 22623978] A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides
[PMID 21362310] Polymorphism on chromosome 9p21. 3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients
[PMID 22856164] [Evaluation of association between 9 genetic polymorphism and myocardial infarction in the Siberian population]
[PMID 18224312] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
[PMID 18533027] Worldwide population differentiation at disease-associated SNPs.
[PMID 18599798] Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis.
[PMID 18654002] Validation of the association of genetic variants on chromosome 9p21 and 1q41 with myocardial infarction in a Japanese population.
[PMID 18704761] Molecular genetics of myocardial infarction.
[PMID 18780302] Association studies of 22 candidate SNPs with late-onset Alzheimer's disease.
[PMID 18852197] Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
[PMID 18925945] Lack of association of two common polymorphisms on 9p21 with risk of coronary heart disease and myocardial infarction; results from a prospective cohort study.
[PMID 18957718] Chromosome 9p21.3 is associated with early-onset coronary heart disease in the Irish population.
[PMID 18987759] Genetic testing for atherosclerosis risk: inevitability or pipe dream?
[PMID 19135198] Evaluation of the association of genetic variants on the chromosomal loci 9p21.3, 6q25.1, and 2q36.3 with angiographically characterized coronary artery disease.
[PMID 19173706] The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis.
[PMID 19214202] Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.
[PMID 19329499] A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study.
[PMID 19343170] INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
[PMID 19463184] Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease.
[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
[PMID 19475673] Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.
[PMID 19578366] Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.
[PMID 19664850] Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer's disease.
[PMID 19750184] Genome-wide association studies for atherosclerotic vascular disease and its risk factors.
[PMID 19885677] The transcription factor GATA-2 does not associate with angiographic coronary artery disease in the Ottawa Heart Genomics and Cleveland Clinic GeneBank Studies.
[PMID 19888323] Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
[PMID 19924713] Use of longitudinal data in genetic studies in the genome-wide association studies era: summary of Group 14.
[PMID 19956433] Genetics of coronary artery disease: focus on genome-wide association studies.
[PMID 19956784] Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease.
[PMID 20017983] Evaluation of population impact of candidate polymorphisms for coronary heart disease in the Framingham Heart Study Offspring Cohort.
[PMID 20031540] Association between the coronary artery disease risk locus on chromosome 9p21.3 and abdominal aortic aneurysm.
[PMID 20098575] Genetics and cardiovascular disease: Design and development of a DNA biobank.
[PMID 20335276] PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.
[PMID 20386740] Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.
[PMID 20395598] Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans.
[PMID 20400779] A common variant at chromosome 9P21.3 is associated with age of onset of coronary disease but not subsequent mortality.
[PMID 20502693] Genetics and beyond--the transcriptome of human monocytes and disease susceptibility.
[PMID 20670758] Gene dosage of the common variant 9p21 predicts severity of coronary artery disease.
[PMID 20923989] Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: A Genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls.
[PMID 21558165] Genetic association of polymorphism rs1333049 with gout.
[PMID 21804106] Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration.
[PMID 22396608] No evidence for association of Chr 9p21 variant rs1333049 with gout in New Zealand case-control sample sets.
[PMID 22436605] Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies.
[PMID 22505696] Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9p21.3 region in patients with rheumatoid arthritis and cardiovascular disease.
|qualified_impact||Insufficiently evaluated pathogenic|
[PMID 23086272] Association between 9p21.3 genomic markers and coronary artery disease in East Asians: a meta-analysis involving 9,813 cases and 10,710 controls
[PMID 23266621] Association of ANRIL polymorphism (rs1333049:C>G) with myocardial infarction and its pharmacogenomic role in hypercholesterolemia
[PMID 23535969] Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome
[PMID 23587283] Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four U.S. populations: The Population Architecture using Genomics and Epidemiology (PAGE) study
[PMID 23142796] An Italian association study and meta-analysis with previous GWAS confirm WNT4, CDKN2BAS and FN1 as the first identified susceptibility loci for endometriosis
[PMID 23787071] Association of arterial stiffness with single nucleotide polymorphism rs1333049 and metabolic risk factors
[PMID 23933542] The 9p21 locus does not affect risk of coronary artery disease through induction of type 1 interferons
[PMID 24069144] Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction
[PMID 24163049] The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts
[PMID 24087953] [Genetic predictors of myocardial infarction in subjects of young age]
[PMID 24246088] Variant at 9p21 rs1333049 is associated with age of onset of coronary artery disease in a Western Indian population: a case control association study
[PMID 24573017] Associations between the CDKN2A/B, ADTRP and PDGFD Polymorphisms and the Development of Coronary Atherosclerosis in Japanese Patients
[PMID 23729007] Two chromosome 9p21 haplotype blocks distinguish between coronary artery disease and myocardial infarction risk.
[PMID 25032714] 9p21.3 risk locus is associated with first-ever myocardial infarction in an Austrian cohort
|Trait||Coronary artery disease|
|Title||Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.|
|Odds Ratio||1.24 [1.21-1.28]|