|(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|
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 18775538]
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
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
|Title||Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease|
|Odds Ratio||1.5100 [1.33-1.70]|
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[PMID 18682748] Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.
[PMID 19060906] 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.
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[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.
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[PMID 30594920] Investigation of LPA sequence variants rs6415084, rs3798220 with conventional coronary artery disease in Iranian CAD patients.
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