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

KIF6 基因作为他汀类药物治疗降脂作用的药物遗传学标记

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作者:Cristina Ruiz-Iruela, Ariadna Padró-Miquel, Xavier Pintó-Sala, Neus Baena-Díez, Assumpta Caixàs-Pedragós, Roser Güell-Miró, Rosa Navarro-Badal, Xavier Jusmet-Miguel, Pilar Calmarza, José Luis Puzo-Foncilla, Pedro Alía-Ramos, Beatriz Candás-Estébanez

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

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.

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).

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