|(A;G)||~1.2x increased risk for heart disease|
|(G;G)||~1.3x increased risk for heart disease|
rs10757274 is a SNP located in chromosomal region 9p21; to date (2009), it is the strongest genetic predictor of early myocardial infarction (heart attack) discovered so far. SNPs in this region are also associated with increased risk of stroke, abdominal aortic aneurysm (AAA), and intracranial aneurysm.
Based on a large (20,000+) study primarily of Caucasian females, it appears that on its own, this single SNP does not improve on the discrimination or classification of predicted heart disease risk achieved by traditional risk factors, high-sensitivity C-reactive protein, and a family history of premature myocardial infarction. [PMID 19153409]
rs10757274 and rs2383206 can double the risk of heart disease. About one in every four Caucasians are thought to carry the gene variants. rs10757278 in the same region has been linked to diabetes 
[PMID 18066490] Also found to be significant in a study of 416 Italian myocardial infarction patients.
[PMID 19901189] A study of 492 sudden and/or arrhythmic deaths and 1460 matched controls concluded that each rs10757274(G) allele conferred an odds ratio of about 1.3 for sudden cardiac death (p=0.003-0.001).
- Note: odds ratios cited for genotypes are from [PMID 17478681]
[PMID 19559344] Genetic variants on chromosome 9p21 and ischemic stroke in Chinese
[PMID 20031596] Impact of Adding a Single Allele in the 9p21 Locus to Traditional Risk Factors on Reclassification of Coronary Heart Disease Risk and Implications for Lipid-Modifying Therapy in the Atherosclerosis Risk in Communities Study
[PMID 20031580] Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study
[PMID 19752551] Polymorphisms associated with both noncardioembolic stroke and coronary heart disease: vienna stroke registry
[PMID 21375403] The Relationship Between Polymorphisms on Chromosome 9p21 and Age of Onset of Coronary Heart Disease in Black and White Women
[PMID 21385355] Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry
[PMID 22430189] Replication of relevant SNPs associated with cardiovascular disease susceptibility obtained from GWAs in a case-control study in a Canarian population
[PMID 17767904] Genetic and genomic insights into the molecular basis of atherosclerosis.
[PMID 18250146] Chromosome 9p21.3 coronary heart disease locus genotype and prospective risk of CHD in healthy middle-aged men.
[PMID 18362232] Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.
[PMID 18443000] Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study.
[PMID 18505420] Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest).
[PMID 18599554] Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia.
[PMID 18620593] Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome.
[PMID 18704761] Molecular genetics of myocardial infarction.
[PMID 18987759] Genetic testing for atherosclerosis risk: inevitability or pipe dream?
[PMID 19019192] Association of genetic variation on chromosome 9p21.3 and arterial stiffness.
[PMID 19171343] Lack of association of chromosome 9p21.3 genotype with cardiovascular structure and function in persons with stable coronary artery disease: The Heart and Soul Study.
[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 19750184] Genome-wide association studies for atherosclerotic vascular disease and its risk factors.
[PMID 19888323] Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
[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 20075150] Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.
[PMID 20386740] Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.
[PMID 20718794] Association of polymorphisms in 9p21 region with CAD in North Indian population: replication of SNPs identified through GWAS.
[PMID 21804106] Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration.
[PMID 22034006] Variants on chromosome 9p21.3 correlated with ANRIL expression contribute to stroke risk and recurrence in a large prospective stroke population.
[PMID 23249639] Association between a Marker on Chromosome 9 and Acute Coronary Syndrome. Confirmatory Study on Czech Population
[PMID 23388737] Association of Single Nucleotide Polymorphisms on Chromosome 9p21.3 With Cardiovascular Death in Kidney Transplant Recipients
[PMID 23535969] Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome
|Trait||Coronary heart disease|
|Title||Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease.|
|Odds Ratio||1.37 [1.31-1.43]|
[PMID 22935634] Effect of 9p21 genetic variation on coronary heart disease is not modified by other risk markers. The Atherosclerosis Risk in Communities (ARIC) Study.
[PMID 22975211] Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary artery disease.
[PMID 26109989] The cardiovascular implication of single nucleotide polymorphisms of chromosome 9p21 locus among Arab population
[PMID 26944720] Polymorphisms in the long non-coding RNA CDKN2B-AS1 may contribute to higher systolic blood pressure levels in hypertensive patients.
[PMID 28057453] Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients.
[PMID 29905076] Genetic Variation in 9p21 and the Plasma Proteome.
[PMID 31472045] Common SNP-based haplotype analysis of the 9p21.3 gene locus as predictor coronary artery disease in Tanzanian population.