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Influence of APOA5 Locus on the Treatment Efficacy of Three Statins: Evidence From a Randomized Pilot Study in Chinese Subjects

机译:APOA5基因座对三种他汀类药物治疗功效的影响:来自中国受试者的随机先导研究的证据

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摘要

Pharmacogenetics or pharmacogenomics approaches are important for addressing the individual variabilities of drug efficacy especially in the era of precision medicine. One particular interesting gene to investigate is APOA5, which has been repeatedly linked with the inter-individual variations of serum triglycerides. Here, we explored APOA5-statin interactions in 195 Chinese subjects randomized to rosuvastatin (5–10 mg/day), atorvastatin (10–20 mg/day), or simvastatin (40 mg/day) for 12 weeks by performing a targeted genotyping analysis of the APOA5 promoter SNP rs662799 (-1131T > C). There were no significant differences between the treatment arms for any of the statin-induced changes in clinical biomarkers. Reductions in LDL cholesterol were influenced by the APOA5 genotype in all three treatment groups. By contrast, changes in HDL cholesterol, and triglycerides were only affected by the APOA5 genotype in the atorvastatin and simvastatin groups and not in the rosuvastatin group. Our results suggest that future studies may need to consider stratifying subjects not only by genetic background but also by prescribed statin type.
机译:药物遗传学或药物基因组学方法对于解决药物功效的个体差异非常重要,尤其是在精密医学时代。一个值得研究的特别有趣的基因是APOA5,它已与血清甘油三酸酯的个体间差异反复联系在一起。在这里,我们通过进行针对性的基因分型,探讨了随机分组于瑞舒伐他汀(5-10 mg /天),阿托伐他汀(10-20 mg /天)或辛伐他汀(40 mg /天)的195位中国受试者中APOA5-他汀类药物的相互作用,持续12周。 APOA5启动子SNP rs662799(-1131T> C)的序列分析。在他汀类药物引起的临床生物标志物变化方面,治疗组之间无显着差异。在所有三个治疗组中,LDL胆固醇的降低均受APOA5基因型的影响。相比之下,阿托伐他汀和辛伐他汀组的HDL胆固醇和甘油三酸酯的变化仅受APOA5基因型的影响,而瑞舒伐他汀组则不受APOA5基因型的影响。我们的结果表明,未来的研究可能不仅需要根据遗传背景,还应根据处方的他汀类药物类型对受试者进行分层。

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