Giannakopoulou E, Ragia G, Kolovou V, Tavridou A, Tselepis A D, Elisaf M, Kolovou G, Manolopoulos V G
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100, Alexandroupolis, Greece.
Mol Biol Rep. 2014 Jul;41(7):4631-8. doi: 10.1007/s11033-014-3334-z. Epub 2014 Mar 26.
Interindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors. Organic anion-transporting polypeptide 1B1 (OATP1B1) encoded by SLCO1B1 gene (solute carrier organic anion transporter family member 1B1) facilitates hepatic uptake of simvastatin and atorvastatin. SLCO1B1 polymorphisms are strongly associated with statin-induced myopathy whereas few studies have assessed their effect on statin differential response. In the present study, we analyzed the association of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms with response to atorvastatin and simvastatin in 386 adults (201 atorvastatin-treated and 185 simvastatin-treated) with primary hypercholesterolemia, all of Greek origin. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment. Genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A novel RFLP protocol was developed for the simultaneous identification of 388A>G and 411G>A polymorphisms. SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms were not associated with lipid-lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene interaction was observed on the effect of the analyzed SLCO1B1 polymorphisms in statin lipid lowering response in either statin-treated patient cohort. Further studies in different populations are required to draw firm conclusion on the potential association of SLCO1B1 polymorphisms with statin lipid-lowering response.
他汀类药物的降脂反应存在个体差异,部分原因是遗传因素。溶质载体有机阴离子转运体家族成员1B1(SLCO1B1)基因编码的有机阴离子转运多肽1B1(OATP1B1)促进辛伐他汀和阿托伐他汀的肝脏摄取。SLCO1B1基因多态性与他汀类药物引起的肌病密切相关,而很少有研究评估它们对他汀类药物差异反应的影响。在本研究中,我们分析了386名原发性高胆固醇血症成年患者(201名接受阿托伐他汀治疗,185名接受辛伐他汀治疗)中SLCO1B1基因521T>C、388A>G和411G>A多态性与阿托伐他汀和辛伐他汀反应之间的关联,所有患者均为希腊裔。在基线和治疗6个月时测量总胆固醇和低密度脂蛋白胆固醇。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析基因多态性。开发了一种新的RFLP方案用于同时鉴定388A>G和411G>A多态性。SLCO1B1基因521T>C、388A>G和411G>A多态性与阿托伐他汀或辛伐他汀的降脂反应无关。在任何一个他汀类药物治疗的患者队列中,分析的SLCO1B1基因多态性对他汀类药物降脂反应的影响均未观察到性别-基因或他汀类药物剂量-基因相互作用。需要在不同人群中进行进一步研究,以就SLCO1B1基因多态性与他汀类药物降脂反应之间的潜在关联得出确切结论。