This SNP, rs10757278, is one of several clustered together in a region of chromosome 9 that has been linked to increased risk for heart disease and potentially diabetes. The overall estimate of heart disease cases that may involve this SNP (or related ones nearby) is said to be 20-30%.
The risk allele, rs10757278(G), shows an increased association for myocardial infarctions ("MI"; heart attacks) both in general and more specifically in so-called early onset MI. The odds ratio relative to rs10757278(A:A) "noncarrier" individuals for rs10757278(G;G) individuals is 1.64 (CI: 1.47-1.82), and for carriers of one risk allele, i.e. rs10757278(A;G) individuals, 1.26 (CI: 1.16-1.36). [PMID 17478679]
For early onset MI, the odds are slightly higher; homozygote rs10757278(G;G) individuals have an odds ratio of 2.02 (CI: 1.72-2.36), heterozygote rs10757278(A;G) individuals 1.49 (CI: 1.31-1.69) compared to noncarriers. To put it another way, men under the age of 50 and women under the age of 60 who are rs10757278(G:G) individuals have about twice the risk of having a heart attack compared to rs10757278(A:A) individuals. [PMID 17478679]
In an extension of the research reported above, the rs10757278(G) allele has been found to be associated with stroke as defined by abdominal aortic aneurysm (AAA; odds ratio 1.31, p=1.2x10e-12) and intracranial aneurysm (odds ratio 1.29, p=2.5x10e-6), but not with type-2 diabetes. The AA genotype appears to be protective, with 0.77x odds of developing abdominal aortic aneurysm as reported by DeCode. [PMID 18176561]
[PMID 18066490] Also found to be significant in a study of 416 Italian myocardial infarction patients.
- Note: this SNP and rs1333049 are practically equivalent, with linkage r2=1 in HapMap CEU populations
[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 19293724] The myocardial infarction associated CDKN2A/CDKN2B locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension
[PMID 19805338] A quantitative model for age-dependent expression of the p16INK4a tumor suppressor
[PMID 20031606] The 9p21 Myocardial Infarction Risk Allele Increases Risk of Peripheral Artery Disease in Older People
[PMID 20031605] 9p21 is a Shared Susceptibility Locus Strongly for Coronary Artery Disease and Weakly for Ischemic Stroke in Chinese Han Population
[PMID 20190001] The Relationship Between Smoking and Replicated Sequence Variants on Chromosomes 8 and 9 With Familial Intracranial Aneurysm
[PMID 20305218] C-B3-03: Association of Epidemiologic and Genetic Factors With Abdominal Aortic Aneurysm (AAA)
The association remained significant after adjusting for significant clinical covariates (P=0.001 to 0.024). We identified one risk haplotype (GGGG; P=0.017) and one protective haplotype (AAAA; P=0.007) for development of CAD. Further analysis suggested that the SNPs probably confer susceptibility to CAD in a dominance model (covariates-adjusted P=0.001 to 0.024; OR=2.37 to 1.54).
[PMID 20729229] The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease
[PMID 20871623] Genetic analysis of six SNPs in candidate genes associated with high cross-race risk of development of thoracic aortic aneurysms and dissections in Chinese Han population
[PMID 21088391] Exploration of a Hypothesized Independent Association of a Common 9p21.3 Gene Variant and Ischemic Stroke in Patients with and without Angiographic Coronary Artery Disease
[PMID 21315566] Type 2 diabetes and polymorphisms on chromosome 9p21: A meta-analysis
[PMID 21444365] Association of a sequence variant in DAB2IP with coronary heart disease
[PMID 21511257] The chromosome 9p21 region and myocardial infarction in a European population
[PMID 19860767] Genetic cardiovascular risk factors and age-related macular degeneration
[PMID 21385355] Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry
[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 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 18459066] A common variant on chromosome 9p21 affects the risk of early-onset coronary artery disease.
[PMID 18469204] Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians.
[PMID 18505420] Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest).
[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 18704761] Molecular genetics of myocardial infarction.
[PMID 18854858] Sequence variant on 9p21 is associated with the presence of abdominal aortic aneurysm disease but does not have an impact on aneurysmal expansion.
[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 18987759] Genetic testing for atherosclerosis risk: inevitability or pipe dream?
[PMID 19002430] Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population.
[PMID 19033589] Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes.
[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 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 19359634] Update on the genetics of stroke and cerebrovascular disease 2008.
[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 19503741] Coding variant Met72Thr in the PEDF gene and risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.
[PMID 19578366] Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.
[PMID 19750184] Genome-wide association studies for atherosclerotic vascular disease and its risk factors.
[PMID 19752551] Polymorphisms associated with both noncardioembolic stroke and coronary heart disease: vienna stroke registry.
[PMID 19753309] SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.
[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 20386740] Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.
[PMID 20395606] Chromosome 9p21 in ischemic stroke: population structure and meta-analysis.
[PMID 20395613] Confirmation of an association of single-nucleotide polymorphism rs1333040 on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients.
[PMID 20696043] Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort.
[PMID 20858033] Haplotypes on 9p21 modify the risk for coronary artery disease among Indians.
[PMID 20974651] Association between genetic variation on chromosome 9p21 and aneurysmal subarachnoid haemorrhage.
[PMID 21307941] 9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response.
[PMID 21896860] Association of genetic variation on chromosome 9p21 with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.
[PMID 22034006] Variants on chromosome 9p21.3 correlated with ANRIL expression contribute to stroke risk and recurrence in a large prospective stroke population.
[PMID 22042884] Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study.
[PMID 22198471] Genetic variants at chromosome 9p21, 10p15 and 10q22 and breast cancer susceptibility in a Chinese population.
|qualified_impact||Insufficiently evaluated pathogenic|
|summary||Hom-G mutation here increases risk of abdominal aortic aneurysm mutation by 1.3, Hom-A decreases risk by 1.3.|
[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 23134948] Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)
[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