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约旦人阿托伐他汀反应中多药耐药-1(MDR1)变体的作用。

The role of Multidrug Resistance-1 (MDR1) variants in response to atorvastatin among Jordanians.

机构信息

Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan,

出版信息

Cytotechnology. 2015 Mar;67(2):267-74. doi: 10.1007/s10616-013-9682-z. Epub 2014 Jan 11.

Abstract

The MDR1 gene encodes for P-glycoprotein (P-gp), which is an efflux transporter at the cell membrane. The P-gp has wide substrate specificity for multiple medications including the lipid lowering drug, atorvastatin. In this study, we investigated the possible association between three common MDR1 gene polymorphisms (G2677T, C3435T, and C1236T), and the lipid lowering effect of atorvastatin among Jordanians. Lipid and lipoproteins were measured in blood samples collected from patients (n = 201) at baseline and during atorvastatin treatment. MDR1 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Both the TT genotype of G2677T and the TT genotype of the C3435T polymorphisms were associated with lower levels of low-density lipoproteins after atorvastatin treatment. However, the effects of atorvastatin on the levels of total cholesterol, triglycerides, and high-density lipoprotein, were not correlated with any of the genotypes in both polymorphisms. Finally, the C1236T polymorphism was not associated with the lipid lowering effect of atorvastatin. In conclusion, the MDR1 gene polymorphisms G2677T, and C3435T, but not C1236T were associated with the lipid lowering effect of atorvastatin among Jordanians.

摘要

MDR1 基因编码 P-糖蛋白(P-gp),它是细胞膜上的一种外排转运蛋白。P-gp 对多种药物具有广泛的底物特异性,包括降脂药物阿托伐他汀。在这项研究中,我们调查了三种常见的 MDR1 基因多态性(G2677T、C3435T 和 C1236T)与阿托伐他汀在约旦人群中的降脂作用之间的可能关联。在基线和阿托伐他汀治疗期间,从患者(n=201)的血液样本中测量了血脂和脂蛋白。使用聚合酶链反应-限制性片段长度多态性对 MDR1 多态性进行了基因分型。G2677T 的 TT 基因型和 C3435T 多态性的 TT 基因型与阿托伐他汀治疗后低密度脂蛋白水平降低有关。然而,阿托伐他汀对总胆固醇、甘油三酯和高密度脂蛋白水平的影响与这两种多态性中的任何一种基因型都没有相关性。最后,C1236T 多态性与阿托伐他汀的降脂作用无关。总之,MDR1 基因多态性 G2677T 和 C3435T 与阿托伐他汀在约旦人群中的降脂作用有关,但 C1236T 多态性则没有。

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