KIF6 gene as a pharmacogenetic marker for lipid-lowering effect in statin treatment

• Published in: PloS one 2018-10, Vol.13 (10), p.e0205430-e0205430
• Main Authors: Ruiz-Iruela, Cristina, Padró-Miquel, Ariadna, Pintó-Sala, Xavier, Baena-Díez, Neus, Caixàs-Pedragós, Assumpta, Güell-Miró, Roser, Navarro-Badal, Rosa, Jusmet-Miguel, Xavier, Calmarza, Pilar, Puzo-Foncilla, José Luis, Alía-Ramos, Pedro, Candás-Estébanez, Beatriz
• Format: Article
• Language: English
• Subjects: Agents antilipèmics; Analysis; Anticholesteremic Agents - therapeutic use; Antilipemic agents; Atorvastatin; Atorvastatin - therapeutic use; Biological markers; Biology and Life Sciences; Biomarkers, Pharmacological - blood; Cardiology; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Cholesterol, LDL - blood; Cholesterol, LDL - drug effects; Clinical medicine; Colesterol; DNA - blood; DNA - genetics; Dosage and administration; Drug therapy; Female; Genes; Genetic diversity; Genetic variance; Genetics; Genotypes; Health risks; Heart; High density lipoprotein; Hospitals; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Hyperlipidemia; Kinesins - blood; Kinesins - genetics; Laboratories; Lipids; Low density lipoprotein; Malalties cardiovasculars; Male; Medicine and Health Sciences; Middle Aged; Mutation; Mutation, Missense; Patients; Pharmacogenomic Testing; Pharmacology; Physiological responses; Prescription drugs; Prospective Studies; Rosuvastatin; Rosuvastatin Calcium - therapeutic use; Simvastatin; Simvastatin - therapeutic use; Statins; Studies; Systematic review; Treatment outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0205430

The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T> C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins. The aim of this study was to investigate whether or not the c.2155T> C KIF6 gene variant modulates the hypercholesteremic effects of treatment with simvastatin, atorvastatin, or rosuvastatin. This was a prospective, observational and multicenter study. Three hundred and forty-four patients who had not undergone prior lipid-lowering treatment were recruited. Simvastatin, atorvastatin or rosuvastatin were administered. Lipid profiles and multiple clinical and biochemical variables were assessed before and after treatment. The c.2155T> C variant of the KIF6 gene was shown to influence physiological responses to treatment with simvastatin and atorvastatin. Patients who were homozygous for the c.2155T> C variant (CC genotype, ArgArg) had a 7.0% smaller reduction of LDL cholesterol levels (p = 0.015) in response to hypolipidemic treatment compared to patients with the TT (TrpTrp) or CT (TrpArg) genotype. After pharmacological treatment with rosuvastatin, patients carrying the genetic variant had an increase in c-HDL that was 21.9% lower compared to patients who did not carry the variant (p = 0.008). Being a carrier of the c.2155T> C variant of the KIF6 gene negatively impacts patient responses to simvastatin, atorvastatin or rosuvastatin in terms of lipid lowering effect. Increasing the intensity of hypolipidemic therapy may be advisable for patients who are positive for the c.2155T> C variant.