Kolovou Genovefa, Ragia Georgia, Kolovou Vana, Mihas Constantinos, Katsiki Niki, Vasiliadis Ioannis, Mavrogeni Sophie, Vartela Vassiliki, Tavridou Anna, Manolopoulos Vangelis G
Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
Open Cardiovasc Med J. 2014 Feb 7;8:12-7. doi: 10.2174/1874192401408010012. eCollection 2014.
One of the promises of human genetics is individualized therapy. Therefore, we evaluated the impact of CYP3A5 gene polymorphism on the effectiveness of simvastatin (a HMG-CoA reductase inhibitor).
Patients (n = 191) with hypercholesterolemia were treated with simvastatin for at least 6 months and were genotyped for the CYP3A5 polymorphism.
The frequency of CYP3A5 polymorphism was 0.5% for WT (wild-type), 15.6% for HT (heterozygous, expressors) and 83.9% for HM (homozygous, non-expressors). Differences in lipid profile before and after dose-response of simvastatin treatment were described as % difference {[(variable after-variable before)/variable before]*100}. There was a trend towards the decrease of low density lipoprotein cholesterol (LDL-C) in HT individuals who had a -35.2% reduction with a dose of 20 mg simvastatin and HM individuals who had a slightly higher decrease (-37.5%) despite the lower dose of simvastatin (10 mg, p = 0.07). Furthermore, HT genotype individuals had significantly higher than expected (6-8%) LDL-C % difference between 20 and 40 mg of simvastatin (-35.2 vs -49.2%, p = 0.037). In individuals with HM genotype a significant LDL-C % difference was found between 10 and 40 mg of simvastatin (-37.5 vs -48.4%, p = 0.023).
The individuals with HM polymorphism display a trend towards higher LDL-C reductions compared with HT polymorphism. Within the same genotype, differences between doses were also observed. These findings need to be confirmed in larger studies.
人类遗传学的前景之一是个性化治疗。因此，我们评估了CYP3A5基因多态性对辛伐他汀（一种HMG-CoA还原酶抑制剂）疗效的影响。
对191例高胆固醇血症患者用辛伐他汀治疗至少6个月，并对其进行CYP3A5基因多态性基因分型。
CYP3A5基因多态性的频率为野生型（WT）0.5%，杂合子（HT，表达型）15.6%，纯合子（HM，非表达型）83.9%。辛伐他汀治疗剂量反应前后血脂谱的差异用百分比差异描述{[（变量后-变量前）/变量前]×100}。HT个体低密度脂蛋白胆固醇（LDL-C）有下降趋势，服用20mg辛伐他汀时下降35.2%，而HM个体尽管辛伐他汀剂量较低（10mg），下降幅度略高（-37.5%）（p = 0.07）。此外，HT基因型个体在20mg和40mg辛伐他汀之间的LDL-C百分比差异显著高于预期（6-8%）（-35.2%对-49.2%，p = 0.037）。在HM基因型个体中，10mg和40mg辛伐他汀之间发现显著的LDL-C百分比差异（-37.5%对-48.4%，p = 0.023）。
与HT多态性相比，具有HM多态性的个体LDL-C降低趋势更明显。在同一基因型内，也观察到了剂量之间的差异。这些发现需要在更大规模的研究中得到证实。
