{{Rsnum
|rsid=10757278
|Chromosome=9
|position=22124478
|Orientation=plus
|GMAF=0.4279
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 24.1 | 50.0 | 25.9
| HCB | 28.2 | 48.7 | 23.1
| JPT | 27.8 | 38.9 | 33.3
| YRI | 90.2 | 9.8 | 0.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 28.2 | 48.7 | 23.1
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}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}} 

Two other SNPs in this region with similar reports are [[rs10757274]] and [[rs2383206]].

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|18048766}} This SNP was also associated with increased risk for [[coronary artery disease]] in a Korean population.

{{PMID|18066490}} Also found to be significant in a study of 416 Italian myocardial infarction patients.
 
{{PMID|19319159|OA=1
}} A study and meta-analysis of 2,000+ Belgians concluded that [[rs10757278]] is associated with increased risk for [[coronary artery disease]] but not ischemic cerebrovascular disease.

* Note: this SNP and [[rs1333049]] are practically equivalent, with linkage r<sup>2</sup>=1 in HapMap CEU populations

{{ neighbor
| rsid = 1333049
| distance = 1026
}}

{{ neighbor
| rsid = 1333048
| distance = 870
}}
{{GWAS Summary
|SNP=rs10757278
|PubMedID=17478679
|Condition=Myocardial infarction
|Gene=CDKN2A,CDKN2B
|Risk Allele=G
|pValue=1.00E-020
|OR=1.28
|95CI=1.22-1.35
}}
{{PMID Auto
|PMID=19343170
|Title=INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
|OA=1
}}

{{PMID Auto
|PMID=19463184
|Title=Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease
|OA=1
}}

{{omim
|desc=CORONARY HEART DISEASE, SUSCEPTIBILITY TO, 8; CHDS8
|id=611139
|rsnum=10757278
}}

{{omim
|desc=AORTIC ANEURYSM, FAMILIAL ABDOMINAL 3
|id=611891
|rsnum=10757278
}}

{{omim
|desc=ANEURYSM, INTRACRANIAL BERRY, 6
|id=611892
|rsnum=10757278
}}
{{PMID Auto
|PMID=19293724
|Title=The myocardial infarction associated CDKN2A/CDKN2B locus on chromosome 9p21 is associated with stroke independently of coronary events in patients with hypertension
}}
{{PMID Auto
|PMID=19805338
|Title=A quantitative model for age-dependent expression of the p16INK4a tumor suppressor
|OA=1
}}

{{PharmGKB
|RSID=rs10757278
|Name_s=
|Gene_s=-
|Feature=
|Evidence=PubMed ID:17478679; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS Results: A common variant on chromosome 9p21 affects the risk of myocardial infarction (Initial Sample Size: 1,607 cases, 6,728 controls; Replication Sample Size: 2,980 cases, 6,309 controls; Risk Allele: rs10757278-G).
|Drugs=
|Drug Classes=
|Diseases=Myocardial Infarction
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA162356619
}}
{{PMID Auto
|PMID=20031606
|Title=The 9p21 Myocardial Infarction Risk Allele Increases Risk of Peripheral Artery Disease in Older People
|OA=1
}}
{{PMID Auto
|PMID=20031605
|Title=9p21 is a Shared Susceptibility Locus Strongly for Coronary Artery Disease and Weakly for Ischemic Stroke in Chinese Han Population
}}

{{PMID Auto
|PMID=20190001
|Title=The Relationship Between Smoking and Replicated Sequence Variants on Chromosomes 8 and 9 With Familial Intracranial Aneurysm
|OA=1
}}

{{PMID Auto
|PMID=20305218
|Title=C-B3-03: Association of Epidemiologic and Genetic Factors With Abdominal Aortic Aneurysm (AAA)
}}

{{PMID|18048766}} [[coronary artery disease]] [[rs1075727]] and [[rs2383206]]  

{{PMID|18048766}} [[myocardial infarction]] [[rs2383207]] and [[rs10757278]]

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 Auto
|PMID=20729229
|Title=The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease
|OA=1
}}
{{PMID Auto
|PMID=20871623
|Title=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 Auto
|PMID=21088391
|Title=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 Auto
|PMID=21315566
|Title=Type 2 diabetes and polymorphisms on chromosome 9p21: A meta-analysis
}}

{{PMID Auto
|PMID=21444365
|Title=Association of a sequence variant in DAB2IP with coronary heart disease
|OA=1
}}

{{PMID Auto
|PMID=21511257
|Title=The chromosome 9p21 region and myocardial infarction in a European population
}}

{{PMID Auto
|PMID=19860767
|Title=Genetic cardiovascular risk factors and age-related macular degeneration
}}

{{PMID Auto
|PMID=21385355
|Title=Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry
|OA=1
}}

{{PMID Auto
|PMID=22856164
|Title=[Evaluation of association between 9 genetic polymorphism and myocardial infarction in the Siberian population]
}}

{{PMID Auto
|PMID=18224312
|Title=Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
|OA=1
}}

{{PMID Auto
|PMID=18362232
|Title=Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.
|OA=1
}}

{{PMID Auto
|PMID=18443000
|Title=Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study.
|OA=1
}}

{{PMID Auto
|PMID=18459066
|Title=A common variant on chromosome 9p21 affects the risk of early-onset coronary artery disease.
}}

{{PMID Auto
|PMID=18469204
|Title=Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians.
|OA=1
}}

{{PMID Auto
|PMID=18505420
|Title=Four SNPS on chromosome 9p21 confer risk to premature, familial CAD and MI in an American Caucasian population (GeneQuest).
|OA=1
}}

{{PMID Auto
|PMID=18675980
|Title=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.
|OA=1
}}

{{PMID Auto
|PMID=18704761
|Title=Molecular genetics of myocardial infarction.
|OA=1
}}

{{PMID Auto
|PMID=18854858
|Title=Sequence variant on 9p21 is associated with the presence of abdominal aortic aneurysm disease but does not have an impact on aneurysmal expansion.
|OA=1
}}

{{PMID Auto
|PMID=18925945
|Title=Lack of association of two common polymorphisms on 9p21 with risk of coronary heart disease and myocardial infarction; results from a prospective cohort study.
|OA=1
}}

{{PMID Auto
|PMID=18987759
|Title=Genetic testing for atherosclerosis risk: inevitability or pipe dream?
|OA=1
}}

{{PMID Auto
|PMID=19002430
|Title=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 Auto
|PMID=19033589
|Title=Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=19171343
|Title=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.
|OA=1
}}

{{PMID Auto
|PMID=19173706
|Title=The 9p21 susceptibility locus for coronary artery disease and the severity of coronary atherosclerosis.
|OA=1
}}

{{PMID Auto
|PMID=19214202
|Title=Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.
|OA=1
}}

{{PMID Auto
|PMID=19329499
|Title=A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study.
|OA=1
}}

{{PMID Auto
|PMID=19359634
|Title=Update on the genetics of stroke and cerebrovascular disease 2008.
|OA=1
}}

{{PMID Auto
|PMID=19474294
|Title=Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
|OA=1
}}

{{PMID Auto
|PMID=19475673
|Title=Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke.
|OA=1
}}

{{PMID Auto
|PMID=19503741
|Title=Coding variant Met72Thr in the PEDF gene and risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.
|OA=1
}}

{{PMID Auto
|PMID=19578366
|Title=Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility.
|OA=1
}}

{{PMID Auto
|PMID=19750184
|Title=Genome-wide association studies for atherosclerotic vascular disease and its risk factors.
|OA=1
}}

{{PMID Auto
|PMID=19752551
|Title=Polymorphisms associated with both noncardioembolic stroke and coronary heart disease: vienna stroke registry.
|OA=1
}}

{{PMID Auto
|PMID=19753309
|Title=SOD2 gene polymorphisms in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.
|OA=1
}}

{{PMID Auto
|PMID=19888323
|Title=Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
|OA=1
}}

{{PMID Auto
|PMID=19956433
|Title=Genetics of coronary artery disease: focus on genome-wide association studies.
|OA=1
}}

{{PMID Auto
|PMID=19956784
|Title=Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease.
|OA=1
}}

{{PMID Auto
|PMID=20386740
|Title=Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.
|OA=1
}}

{{PMID Auto
|PMID=20395606
|Title=Chromosome 9p21 in ischemic stroke: population structure and meta-analysis.
|OA=1
}}

{{PMID Auto
|PMID=20395613
|Title=Confirmation of an association of single-nucleotide polymorphism rs1333040 on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients.
}}

{{PMID Auto
|PMID=20696043
|Title=Replication of the association of chromosomal region 9p21.3 with generalized aggressive periodontitis (gAgP) using an independent case-control cohort.
|OA=1
}}

{{PMID Auto
|PMID=20858033
|Title=Haplotypes on 9p21 modify the risk for coronary artery disease among Indians.
}}

{{PMID Auto
|PMID=20974651
|Title=Association between genetic variation on chromosome 9p21 and aneurysmal subarachnoid haemorrhage.
}}

{{PMID Auto
|PMID=21307941
|Title=9p21 DNA variants associated with coronary artery disease impair interferon-gamma signalling response.
|OA=1
}}

{{PMID Auto
|PMID=21896860
|Title=Association of genetic variation on chromosome 9p21 with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.
}}

{{PMID Auto
|PMID=22034006
|Title=Variants on chromosome 9p21.3 correlated with ANRIL expression contribute to stroke risk and recurrence in a large prospective stroke population.
}}

{{PMID Auto
|PMID=22042884
|Title=Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study.
|OA=1
}}

{{PMID Auto
|PMID=22198471
|Title=Genetic variants at chromosome 9p21, 10p15 and 10q22 and breast cancer susceptibility in a Chinese population.
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs10757278
|overall_frequency_n=41
|overall_frequency_d=128
|overall_frequency=0.320312
|n_genomes=27
|n_genomes_annotated=0
|n_haplomes=33
|n_articles=1
|n_articles_annotated=1
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
|summary_short=Hom-G mutation here increases risk of abdominal aortic aneurysm mutation by 1.3, Hom-A decreases risk by 1.3.
}}

{{PMID Auto
|PMID=23086272
|Title=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 Auto
|PMID=23134948
|Title=Association between 9p21 genetic variants and mortality risk in a prospective cohort of patients with type 2 diabetes (ZODIAC-15)
|OA=1
}}

[[Brain Aneurysm]]

{{PMID Auto
|PMID=23388737
|Title=Association of Single Nucleotide Polymorphisms on Chromosome 9p21.3 With Cardiovascular Death in Kidney Transplant Recipients
}}

{{PMID Auto
|PMID=23535969
|Title=Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome
}}

{{PMID| 22198471}} in Chinese women no significant [[breast cancer]] association at [[rs1011970]], [[rs10757278]] or [[rs2380205]]

{{PMID Auto
|PMID=24069144
|Title=Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction
|OA=1
}}

{{PMID Auto
|PMID=24087953
|Title=[Genetic predictors of myocardial infarction in subjects of young age]
}}

{{PMID Auto
|PMID=24246088
|Title=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 Auto
|PMID=22946666
|Title=The rs10757278 polymorphism of the 9p21.3 locus is associated with premature coronary artery disease in Polish patients.
|OA=1
}}

{{PMID Auto
|PMID=22975211
|Title=Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary artery disease.
}}

{{PMID Auto
|PMID=23733552
|Title=Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals.
|OA=1
}}

{{PMID Auto
|PMID=24782050
|Title=Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people
}}

{{PMID Auto
|PMID=25105296
|Title=Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction
}}

{{PMID Auto
|PMID=24365123
|Title=Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}