Rs20455

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Orientationminus
Geno Mag Summary
(C;C)
(C;T)
(T;T)
ReferenceGRCh38 38.1/141
Chromosome6
Position39357302
GeneKIF6
is asnp
is mentioned by
dbSNPrs20455
Exacrs20455
PheGenIrs20455
nextbiors20455
hapmaprs20455
1000 genomesrs20455
hgdprs20455
ensemblrs20455
gopubmedrs20455
geneviewrs20455
scholarrs20455
googlers20455
pharmgkbrs20455
gwascentralrs20455
openSNPrs20455
23andMers20455
23andMe allrs20455
SNP Nexus

SNPshotrs20455
SNPdbers20455
MSV3drs20455
GMAF0.4904
Max Magnitude
? (C;C) (C;T) (T;T) 28
rs20455, often called Arg719 or 719Arg, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C).

An extensive 2010 meta-analysis, including over 17,000 patients, suggests this variant does not significantly influence coronary artery disease risk.[PMID 20933357OA-icon.png]

This SNP is one of the 5 used by Celera's genetic risk score (GRS) for coronary heart disease (CHD).

For each of the five variants, the GRS was increased by 1 if the subject was homozygous for the risk variant, unchanged if heterozygous, and decreased by 1 if the individual did not carry the variant. Therefore, individuals carrying all 10 possible risk variants (two copies of each of the five SNPs) were assigned a GRS of 5 and those carrying no risk variants a GRS of -5. A high GRS was defined as 3 or higher. Approximately 4% of the white cohort in ARIC was classified as high risk, and the hazard ratio for CHD after adjustment for traditional risk factors was a significant 1.57 (CI: 1.21-2.04; p<0.001). The results did not reproduce for African American participants.[PMID 18073581]

[PMID 18222354] Carriers of the 719Arg allele of KIF6 have 34% higher risk of myocardial infarction and 24% higher risk of coronary heart disease compared with noncarriers among 25,283 women.

[PMID 18222355] Carriers of 719Arg receive significantly greater benefit from intensive statin therapy than do noncarriers. The benefit from intensive (compared with moderate) statin therapy was significantly greater in the 59% of the 1,778 patients who were carriers (hazard ratio 0.59, CI: 0.45 -0.77) than in those who were noncarriers (HR 0.94, CI: 0.70-1.27; p=0.018 for interaction between 719Arg carrier status and treatment). The absolute risk reduction was 10.0% in carriers versus 0.8% in noncarriers.

[PMID 18222353] Untreated carriers of the rs20455 risk allele had odds ratios for MI or stroke of 1.50 and 1.55 (CI: 1.05-2.15 or 1.14-2.09) in two large clinical trials. Among treated carriers, the absolute risk reduction by pravastatin therapy was 4.9% and 5.5% (CI: 1.81-7.9% or 3.5-7.5%). Therefore, in both trials carriers of a rs20455(C) SNP had an increased risk of coronary events, and statin treatment (in this case, pravastatin) reduced that risk more for such carriers than for noncarriers.

[PMID 20215968] Elderly carriers of a rs20455(C) (719Arg) allele with prior vascular disease received significant benefit from pravastatin; however, no benefit was observed in noncarriers with prior disease or in those without prior disease (carriers or noncarriers).

[PMID 20403483] Across all ethnic groups studied, pravastatin therapy significantly and substantially reduced both fatal coronary events and nonfatal myocardial infarctions only for carriers of the 719Arg allele (and not for noncarriers).



[PMID 19752551OA-icon.png] Polymorphisms associated with both noncardioembolic stroke and coronary heart disease: vienna stroke registry


[PMID 20886236OA-icon.png] Genetic variants in the KIF6 region and coronary event reduction from statin therapy


[PMID 21435211OA-icon.png] Survival bias and drug interaction can attenuate cross-sectional case-control comparisons of genes with health outcomes. An example of the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism versus coronary heart disease


[PMID 22135385] The 719Arg Variant of KIF6 and Cardiovascular Outcomes in Statin-Treated, Stable Coronary Patients of the TNT and IDEAL Prospective Studies


[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 18799872OA-icon.png] Single nucleotide polymorphisms associated with coronary heart disease predict incident ischemic stroke in the atherosclerosis risk in communities study.


[PMID 21458191] No impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study.


[PMID 21810021] Investigation of KIF6 Trp719Arg in a case-control study of coronary artery disease in Western Indians.


GET Evidence
KIF6-W719R
aa_change Trp719Arg
aa_change_short W719R
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.50725
summary



[PMID 23001387] Association of KIF6 variant with lipid level and angiographic coronary artery disease events risk in the Han Chinese population.