Rs10757278

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] 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 r²=1 in HapMap CEU populations

GWAS
SNP	rs10757278
PubMedID	[PMID 17478679]
Condition	Myocardial infarction
Gene	CDKN2A,CDKN2B
Risk Allele	G
pValue	1.00E-020
OR	1.28
95% CI	1.22-1.35

[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)

[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 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