Impact of the 719Arg Variant of KIF6 and Major Cardiovascular Events on Patients who Received Statins: A Systematic Review and Meta-Analysis

Purpose: The purpose of this study was to determine the relationship between Kinesin like protein 6 (KIF6) gene Trp719Arg and major cardiovascular events (MACEs) risk in subjects who received statin therapy. Methods: PubMed, EmBase, and the Cochrane Library were searched from inception through September 2017. The selected studies evaluated the association of Trp719Arg with MACEs in individuals who received statins. Relative risk (RR) and 95% confidence interval (CI) were used to evaluate the effect of statin therapy on MACEs in subjects carrying polymorphisms, and the odds ratio (OR) and 95% CI were used to evaluate the relationship between Trp719Arg and MACE risk in individuals who received statins, using the random-effects model. Results: Seven studies were included (N=48,885). Overall, we found that statin therapy significantly reduced the risk for MACEs in subjects carrying ArgArg (RR: 0.79; 95% CI: 0.69-0.90; P=0.001), ArgTrp (RR: 0.71; 95% CI: 0.60 -0.83; P<0.001), ArgArg+ArgTrp (RR: 0.71; 95% CI: 0.63 -0.81; P<0.001), and TrpTrp (RR: 0.79; 95% CI: 0.73-0.85; P<0.001). Furthermore, there was no significant difference between subjects carrying ArgArg and those carrying TrpTrp (OR: 1.11; 95% CI: 0.92-1.34; P=0.265). However, ArgTrp (OR: 1.29; 95% CI: 1.07-1.55; P=0.007) and ArgArg+ArgTrp (OR: 1.26; 95% CI: 1.05-1.51; P=0.012) were associated with an increased risk for MACEs when compared with TrpTrp. Conclusions: Statin therapy significantly reduced the risk for MACEs in subjects carrier specific KIF6 gene Trp719Arg polymorphisms. Further, subjects carrying ArgTrp or ArgArg+ArgTrp had a greater incidence of MACEs as compared with TrpTrp when they received statins.