Rs1333049

This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB. Additional information is available here

rs1333049 has been reported in a large study to be associated with heart disease, in particular, coronary artery disease.

The risk allele (oriented to the dbSNP entry) is most likely (C); the odds ratio associated with heterozygotes is 1.47 (CI 1.27-1.70), and for homozygotes, 1.9 (CI 1.61-2.24). [PMID 17554300]

This SNP has also been reported to have the highest association of any SNP studied in a subsequent experiment conducted with the resources of the German MI [Myocardial Infarction] Family Study. [PMID 17634449, PMID 18362232]

The initial studies were conducted on Caucasian populations. A subsequent study of Japanese and Korean patients has also found rs1333049 to be associated with increased coronary artery disease risk, with roughly similar odds ratios.[PMID 18264662]

[PMID 18652946] A long-term study of a cohort of 769 individuals finds that the rs1333049(C) allele was associated with:

• prevalent carotid atherosclerosis (odds ratio 1.46, 1.43 or 1.44, from data collected in 1990, 1995, and 2000, respectively, all with CI: ~1.1-1.9);
• progression of atherosclerosis (for example, odds ratio 1.87 (CI: 1.44 to 2.42) during 1995 to 2000);
• incident cardiovascular disease (hazard ratio: 1.37 (CI: 1.05 to 1.79)}.

• Note: this SNP and rs10757278 are practically equivalent, with linkage r²=1 in HapMap CEU populations

[PMID 18979498] rs1333049 1.15x risk associated with both coronary heart disease and stroke

[PMID 19171343] In a cross-sectional study of individuals with stable coronary artery disease, there was no association with cardiovascular structure and function.

[PMID 20231156] A study of 3,000+ patients with acute coronary sydrome (ACS) revealed that those carrying a rs1333049(C) allele were at higher risk for subsequent myocardial infarctions [adjusted hazard ratio 1.48, CI: 1.00-2.19, p = 0.048 and with recurrent MI or cardiac death (adjusted HR 1.58, CI: 1.00-2.48, p = 0.045) within 6 months after an index ACS.

GWAS
SNP	rs1333049
PubMedID	[PMID 17554300]
Condition	Coronary disease
Gene	CDKN2A,CDKN2B
Risk Allele	C
pValue	1.00E-013
OR	1.47
95% CI	1.27-1.70

[PMID 19164808] Large scale association analysis of novel genetic loci for coronary artery disease

[PMID 19548844] Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

[PMID 19709660] Single nucleotide polymorphism on chromosome 9p21 and endothelial progenitor cells in a general population cohort

[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 19955471] Genetic Variants Identified in a European Genome-Wide Association Study That Were Found to Predict Incident Coronary Heart Disease in the Atherosclerosis Risk in Communities Study

[PMID 20031606] A study of 2630 white individuals (mean age, 76.4 years) concluded that the rs1333049(C) allele was associated with increased prevalence of peripheral artery disease. The per allele odds ratio was 1.29 (CI: 1.06 to 1.56, p = 0.012).

[PMID 20031580] Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study

[PMID 19926059] No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents

[PMID 20230275] Preliminary evidence of a genetic association between chromosome 9p21.3 and human longevity

[PMID 20427016] Single nucleotide polymorphism rs1333049 on chromosome 9p21.3 is associated with Alzheimer's disease in Han Chinese

[PMID 20649639] Forearm vasodilator reactivity in homozygous carriers of the 9p21.3 rs1333049 G>C polymorphism

[PMID 20691078] Chromosome 9p21.3 polymorphism in a Chinese Han population is associated with angiographic coronary plaque progression in non-diabetic but not in type 2 diabetic patients

[PMID 21152093] Sex Differential Genetic Effect of Chromosome 9p21 on Subclinical Atherosclerosis

[PMID 21511257] The chromosome 9p21 region and myocardial infarction in a European population

GWAS snp
PMID	[PMID 21606135]
Trait
Title	A Genome-wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease.
Risk Allele	C
P-val	7E-58
Odds Ratio	1.2700 [1.23-1.31]

[PMID 21385355] Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

[PMID 22144573] Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction