Abstract 13192: KIF6, LPA, TAS2R50, and VAMP8 Genetic Variation, Low Density Lipoprotein Cholesterol Lowering Response to Pravastatin, and Heart Disease Risk Reduction in the Elderly
Background: Single nucleotide polymorphisms (SNPs) at the KIF6 (kinesin like protein 6, rs20455 or 719Arg), LPA (lipoprotein(a), rs3798220), TAS2R50 (taste receptor type 2, member 50, rs1376251) and VAMP8 (vesicle-associated membrane protein 8, rs1010) have previously been associated with low density lipoprotein (LDL) cholesterol lowering response to statins, cardiovascular disease (CVD) at baseline, or CVD events on trial. KIF6 genotyping is offered commercially as a means of determining who would get benefit from statin therapy in terms of CVD risk reduction.
Methods: We examined SNPs at the KIF6 (rs20455 or 719Arg), LPA (rs3798220), TAS2R50 (rs1376251) and VAMP8 (rs1010) in 5411 participants in PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and were followed for a mean of 3.2 years.
Results: No SNP was related to vascular disease at baseline. Only the KIF6 SNP was related to LDL cholesterol lowering with homozygous Arg 719 subjects being significantly less responsive than other groups (p=0.025, -34.2 vs. -36.1%). With regard to the primary CVD endpoint on trial (fatal or non-fatal myocardial infarction or stroke), we observed a significant relationship for KIF6 719Arg homozygotes (p=0.03, hazards ratio 0.47, 12.8% of the population) in women on pravastatin only, and for TAS2R50 for the AA genotype (p=0.03, hazards ratio 1.76, 8.9% of the population), also only in women on pravastatin.
Conclusions: Our data indicate that the assessment of KIF6 rs20455 and TAS2R50 rs1376251 genotypes is not useful for predicting statin induced cardiovascular risk reduction in men, and predicts CVD risk reduction only in women in this elderly population. This type of genotyping would affect about 13% of the female population with regard to KIF6 genotyping, and about 9% of the female population with regard to TAS2R50 genotyping, and in our view would only be useful in elderly women either with established CVD or at high risk for CVD.
- © 2011 by American Heart Association, Inc.