KIF6 Trp719Arg polymorphism and the effect of statin therapy in elderly patients: results from the PROSPER study.
BACKGROUND
Statin therapy has been found to substantially and significantly reduce coronary events in carriers of the KIF6 719Arg variant (rs20455) but not in noncarriers. We investigated whether, among the elderly, statin therapy also significantly reduced coronary events in carriers but not in noncarriers.


METHODS
Among 5,752 patients of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study, we assessed the effect of pravastatin, compared with placebo, on coronary events according to 719Arg carrier status using proportional hazards models.


RESULTS
Since benefit from statin therapy in elderly patients has been primarily shown among those with prior vascular disease, we performed analyses in PROSPER patients with prior disease and found that pravastatin therapy significantly reduced events in 719Arg carriers [hazards ratio (HR): 0.66, 95% confidence interval (CI): 0.52-0.86] but not in noncarriers (HR: 0.94, 95% CI: 0.69-1.28), P=0.09 for interaction between treatment and carrier status. Among those without prior disease, no significant benefit was observed in either carriers or noncarriers. Among those with prior vascular disease in the placebo arm, Trp719Arg heterozygotes were at significantly greater risk, compared with noncarriers (HR: 1.36, 95% CI: 1.03-1.81, P=0.03); the HR of 719Arg carriers, compared with noncarriers, was 1.28 (95% CI: 0.98-1.69, P=0.07).


CONCLUSIONS
Elderly carriers of the KIF6 719Arg variant with prior vascular disease received significant benefit from pravastatin therapy; no benefit was observed in noncarriers with prior disease or in those without prior disease (carriers or noncarriers).
Iakoubova
Olga A
OA
Celera, Inc., 1401 Harborbay Pkwy, Alameda, CA 94502, USA. olga.iakoubova@celera.com
Robertson
Michele
M
Tong
Carmen H
CH
Rowland
Charles M
CM
Catanese
Joseph J
JJ
Blauw
Gerard J
GJ
Jukema
J W
JW
Murphy
Michael B
MB
Devlin
James J
JJ
Ford
Ian
I
Shepherd
James
J
D000367:Age Factors; D000368:Aged; D003327:Coronary Disease / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016547:Kinesins / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C526774:KIF6 protein, human; D016547:Kinesins; D017035:Pravastatin