Clinical laboratory, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
Cardiovascular unit, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
PLoS One. 2018 Oct 10;13(10):e0205430. doi: 10.1371/journal.pone.0205430. eCollection 2018.
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.
他汀类药物的治疗反应在降低血浆 LDL-胆固醇（c-LDL）和增加 HDL 胆固醇（c-HDL）方面具有很高的个体间变异性。许多研究表明，rs20455 KIF6 基因变异（c.2155T>C，Trp719Arg）与接受他汀类药物治疗的患者心血管疾病风险降低之间存在关系。
本研究旨在探讨 c.2155T>C KIF6 基因变异是否调节辛伐他汀、阿托伐他汀或瑞舒伐他汀治疗的高胆固醇血症作用。
这是一项前瞻性、观察性和多中心研究。招募了 344 名未接受过降脂治疗的患者。给予辛伐他汀、阿托伐他汀或瑞舒伐他汀治疗。在治疗前后评估了血脂谱和多个临床及生化变量。
KIF6 基因的 c.2155T>C 变异与辛伐他汀和阿托伐他汀治疗的生理反应有关。与 TT（TrpTrp）或 CT（TrpArg）基因型的患者相比，纯合 c.2155T>C 变异（CC 基因型，ArgArg）的患者在降脂治疗后 LDL 胆固醇水平降低 7.0%（p=0.015）。在接受瑞舒伐他汀的药物治疗后，携带遗传变异的患者的 c-HDL 增加幅度比不携带变异的患者低 21.9%（p=0.008）。
携带 KIF6 基因的 c.2155T>C 变异会对患者对辛伐他汀、阿托伐他汀或瑞舒伐他汀的反应产生负面影响，表现在降脂作用方面。对于携带 c.2155T>C 变异的患者，增加降脂治疗的强度可能是明智的。
