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Observational Study
. 2018 Oct 10;13(10):e0205430.
doi: 10.1371/journal.pone.0205430. eCollection 2018.

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

Cristina Ruiz-Iruela  1 , Ariadna Padró-Miquel  1 , Xavier Pintó-Sala  2 , Neus Baena-Díez  3 , Assumpta Caixàs-Pedragós  4 , Roser Güell-Miró  5 , Rosa Navarro-Badal  5 , Xavier Jusmet-Miguel  6 , Pilar Calmarza  7 , José Luis Puzo-Foncilla  7 , Pedro Alía-Ramos  1 , Beatriz Candás-Estébanez  1
Affiliations
Observational Study

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

Cristina Ruiz-Iruela et al. PLoS One. .

Abstract

Introduction: 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.

Aim: 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.

Materials and methods: 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.

Results: 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).

Conclusion: 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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Changes in serum c-LDL after treatment stratified by genotypes.
TT = homozygous TrpTrp; TC = heterozygous TrpArg; CC = homozygous ArgArg.
Fig 2
Fig 2. Changes in serum c-Non-HDL after treatment stratified by genotypes.
TT = homozygous TrpTrp; TC = heterozygous TrpArg; CC = homozygous ArgArg.
Fig 3
Fig 3. Changes in serum c-HDL after treatment stratified by genotypes.
TT = homozygous TrpTrp; TC = heterozygous TrpArg; CC = homozygous ArgArg.
See this image and copyright information in PMC

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