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From SNPedia

Geno Mag Summary
(C;C) 2.6 2-3x higher risk for cardiovascular events, which can be lowered by aspirin
(C;T) 2.3 2-3x higher risk for cardiovascular events, which can be lowered by aspirin
(T;T) 0 normal
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
dbSNP (old)rs3798220
1000 genomesrs3798220
23andMe allrs3798220
SNP Nexus

GWAS Ctlgrs3798220
Max Magnitude2.6
? (C;C) (C;T) (T;T) 28
rs3798220, also known as I4399M or Ile4399Met, is a SNP in the apolipoprotein(A) LPA gene that has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk, and in particular, coronary artery disease.

In one study, 25,131 initially healthy Caucasian participants in the Women's Health Study were followed for ~10 years. rs3798220(C) allele carriers (3.7%) in the placebo (i.e. not receiving aspirin) group had a 2x higher risk of major cardiovascular events than non-carriers (age-adjusted hazard ratio (HR) of 2.21, CI: 1.39-3.52). Among rs3798220(C) carriers, the risk was reduced more than twofold by aspirin: for aspirin compared with placebo the age-adjusted HR was 0.44 (CI: 0.20-0.94). The risk was not significantly reduced among non-carriers (age-adjusted HR=0.91, CI: 0.77-1.08). This interaction between carrier status and aspirin allocation was significant (P=0.048). In summary, rs3798220(C) carriers had higher plasma lipoprotein(a) and had double the risk of cardiovascular events, but also benefited more from taking aspirin.[PMID 18775538OA-icon.png]

In another study, compared with noncarriers, carriers of the 4399M risk allele (2.7% of controls) had an adjusted odds ratio for severe CAD of 3.14 (CI: 1.51 to 6.56), and had 5-fold higher median plasma lipoprotein(a) levels (P=0.003), leading to the conclusion that the LPA I4399M SNP is associated with severe CAD and plasma lipoprotein(a) levels.[PMID 17569884]

[PMID 20032323] Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease

celera says rs3798220 is an independent predictor of risk for

Carriers of the rs3798220(C) have higher levels of plasma Lp(a).

[PMID 20605575] Single variants can explain the association between coronary heart disease and haplotypes in the apolipoprotein(a) locus

GWAS snp
PMID [PMID 21378990OA-icon.png]
Title Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
Risk Allele C
P-val 3E-11
Odds Ratio 1.5100 [1.33-1.70]

[PMID 22192511] KIF6, LPA, TAS2R50, and VAMP8 genetic variation, low density lipoprotein cholesterol lowering response to pravastatin, and heart disease risk reduction in the elderly

[PMID 18682748OA-icon.png] Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

[PMID 19060906OA-icon.png] Common variants at 30 loci contribute to polygenic dyslipidemia.

[PMID 19880117] The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles.

[PMID 21252144] Lipoprotein(a) genetic variants associated with coronary and peripheral vascular disease but not with stroke risk in the Heart Protection Study.

[PMID 21283670OA-icon.png] Single-nucleotide polymorphisms in LPA explain most of the ancestry-specific variation in Lp(a) levels in African Americans.

[PMID 22560621] Cost-effectiveness model of use of genetic testing as an aid in assessing the likely benefit of aspirin therapy for primary prevention of cardiovascular disease.

GET Evidence
aa_change Ile1891Met
aa_change_short I1891M
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.0160811
summary This variant strongly associated with an increase in Lp(a) lipoprotein levels, associated with an increased risk of coronary disease in a dominant or incomplete dominant manner. This variant is also referred to as I4399M in literature; this discrepancy is due to a highly variable number of kringle repeats in the protein (2-43), our version for inferring amino acid changes from genetic variants uses an assembly with 15 copies.

[PMID 23735648] Validation and Quantification of Genetic Determinants of Lipoprotein-a Levels and Predictive Value for Angiographic Coronary Artery Disease

[PMID 23978127OA-icon.png] Lack of association between lipoprotein(a) genetic variants and subsequent cardiovascular events in Chinese Han patients with coronary artery disease after percutaneous coronary intervention

[PMID 24161338] Elevated Lipoprotein(a) and Risk of Aortic Valve Stenosis in the General Population

[PMID 22898070] Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism.

[PMID 23100282OA-icon.png] Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.

[PMID 23278389] Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein(A) gene.

[PMID 23375930] Extreme lipoprotein(a) levels and improved cardiovascular risk prediction.

[PMID 24776095OA-icon.png] LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography

[PMID 26302166] Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians

[PMID 26564469] Advances in the Association between Apolipoprotein(a)Gene Polymorphisms and Coronary Heart Disease

[PMID 27831500] The LPA Gene, Ethnicity, and Cardiovascular Events.

[PMID 28566218] Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study.

[PMID 28632940] Characterization of the I4399M variant of apolipoprotein(a): Implications for altered prothrombotic properties of lipoprotein(a).