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 20933357]
- rs20455, in the KIF6 gene
- rs3900940, in the MYH15 gene
- rs7439293, in the PALLD gene
- rs2298566, in the SNX19 gene
- rs1010, in the VAMP8 gene
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 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 19752551] Polymorphisms associated with both noncardioembolic stroke and coronary heart disease: vienna stroke registry
[PMID 20886236] Genetic variants in the KIF6 region and coronary event reduction from statin therapy
[PMID 21435211] 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 18799872] 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.
|qualified_impact||Insufficiently evaluated pharmacogenetic|