|(A;A)||1.9||0.78x reduced risk for Coronary Heart Disease. 0.77x reduced risk for Brain Aneurysm and Abdominal Aortic Aneurysm.|
|(A;G)||2||1.3x risk for Heart Attack. Normal risk for Abdominal Aortic Aneurysm and Brain Aneurysm.|
|(G;G)||2.5||1.6x risk for Heart Attack; 1.3x risk for Abdominal Aortic Aneurysm and Brain Aneurysm.|
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 19293724] The myocardial infarction associated CDKN2A/CDKN2B locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension
[PMID 19463184] Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease
[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
[PMID 24069144] Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction
[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 22946666] The rs10757278 polymorphism of the 9p21.3 locus is associated with premature coronary artery disease in Polish patients.
[PMID 22975211] Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary artery disease.
[PMID 23733552] Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals.
[PMID 24782050] Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people
[PMID 25105296] Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction
[PMID 24365123] Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population
[PMID 25724239] Sequence Variants on Chromosome 9p21 are Associated with Ischemic Stroke and the Lipids Level in Chinese Han Population
[PMID 26109989] The cardiovascular implication of single nucleotide polymorphisms of chromosome 9p21 locus among Arab population
[PMID 26615606] The 9p21 polymorphism is linked with atrial fibrillation during acute phase of ST-segment elevation myocardial infarction.
[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.