细胞色素P450 3A5（CYP3A5）基因多态性对辛伐他汀疗效的影响
Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin.
作者信息
Kolovou Genovefa, Ragia Georgia, Kolovou Vana, Mihas Constantinos, Katsiki Niki, Vasiliadis Ioannis, Mavrogeni Sophie, Vartela Vassiliki, Tavridou Anna, Manolopoulos Vangelis G
机构信息
Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
出版信息
Open Cardiovasc Med J. 2014 Feb 7;8:12-7. doi: 10.2174/1874192401408010012. eCollection 2014.
BACKGROUND
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).
METHODS
Patients (n = 191) with hypercholesterolemia were treated with simvastatin for at least 6 months and were genotyped for the CYP3A5 polymorphism.
RESULTS
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).
CONCLUSION
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.
背景
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。
方法
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。
结果
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）。
结论
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。
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