Rs20455

From SNPedia

rs20455, often called Arg719, is a reasonably well studied SNP in the KIF6 gene. The risk allele (encoding the arginine at position 719) is rs20455(C).

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

• 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 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.