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

被引:10
作者
Alzoubi, Karem H. [1 ]
Khabour, Omar F. [2 ]
Al-azzam, Sayer I. [1 ]
Mayyas, Fadia [1 ]
Mhaidat, Nizar M. [1 ]
机构
[1] Jordan Univ Sci & Technol, Dept Clin Pharm, Fac Pharm, Irbid 22110, Jordan
[2] Jordan Univ Sci & Technol, Dept Med Lab Sci, Irbid 22110, Jordan
关键词
Atorvastatin; MDR1; SNP; Drug response; Jordan; P-GLYCOPROTEIN EXPRESSION; GENETIC POLYMORPHISMS; LOWERING RESPONSE; EPITHELIAL-CELLS; AFRICAN; PHARMACOKINETICS; IDENTIFICATION; TRANSPORTERS; CHOLESTEROL; POPULATION;
D O I
10.1007/s10616-013-9682-z
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:267 / 274
页数:8
相关论文
共 40 条
[1]   CYP2C9, CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a Black Beninese population [J].
Allabi, AC ;
Gala, JL ;
Horsmans, Y .
PHARMACOGENETICS AND GENOMICS, 2005, 15 (11) :779-786
[2]   CYP3A5 and MDR1 genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation [J].
Anglicheau, D ;
Thervet, E ;
Etienne, I ;
De Ligny, BH ;
Le Meur, Y ;
Touchard, G ;
Büchler, M ;
Laurent-Puig, P ;
Tregouet, D ;
Beaune, P ;
Daly, A ;
Legendre, C ;
Marquet, P .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2004, 75 (05) :422-433
[3]   MDR1 3435T and 1236T alleles delay disease progression to pediatric AIDS but have no effect on HIV-1 vertical transmission [J].
Bellusci, Carolina P. ;
Rocco, Carlos A. ;
Aulicino, Paula C. ;
Mecikovsky, Debora ;
Bologna, Rosa ;
Sen, Luisa ;
Mangano, Andrea .
AIDS, 2010, 24 (06) :833-840
[4]   Characterization of the human MDR1 gene [J].
Bodor, M ;
Kelly, EJ ;
Ho, RJ .
AAPS JOURNAL, 2005, 7 (01) :E1-E5
[5]  
Cascorbi I, 2011, HANDB EXP PHARMACOL, V201, P261, DOI 10.1007/978-3-642-14541-4_6
[6]   MDR1 and CYP3A4 polymorphisms among African, Indian, and white populations in KwaZulu-Natal, South Africa [J].
Chelule, PK ;
Gordon, M ;
Palanee, T ;
Page, T ;
Mosam, A ;
Derm, FC ;
Coovadia, HM ;
Cassol, S .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2003, 74 (02) :195-196
[7]   Effects of azithromycin on the expression of ATP binding cassette transporters in epithelial cells from the airways of cystic fibrosis patients [J].
Cigana, C. ;
Nicolis, E. ;
Pasetto, M. ;
Assael, B. M. ;
Melotti, P. .
JOURNAL OF CHEMOTHERAPY, 2007, 19 (06) :643-649
[8]   Drug Transporters in Drug Efficacy and Toxicity [J].
DeGorter, M. K. ;
Xia, C. Q. ;
Yang, J. J. ;
Kim, R. B. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 52, 2012, 52 :249-273
[9]   Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a) [J].
Deshmukh, Harshal A. ;
Colhoun, Helen M. ;
Johnson, Toby ;
McKeigue, Paul M. ;
Betteridge, D. John ;
Durrington, Paul N. ;
Fuller, John H. ;
Livingstone, Shona ;
Charlton-Menys, Valentine ;
Neil, Andrew ;
Poulter, Neil ;
Sever, Peter ;
Shields, Denis C. ;
Stanton, Alice V. ;
Chatterjee, Aurobindo ;
Hyde, Craig ;
Calle, Roberto A. ;
DeMicco, David A. ;
Trompet, Stella ;
Postmus, Iris ;
Ford, Ian ;
Jukema, J. Wouter ;
Caulfield, Mark ;
Hitman, Graham A. .
JOURNAL OF LIPID RESEARCH, 2012, 53 (05) :1000-1011
[10]   Polymorphisms and haplotypes in multidrug resistance 1 gene are not associated with chronic lymphocytic leukemia susceptibility and prognostic parameters of chronic lymphocytic leukemia in Chinese population [J].
Dong, Hua-Jie ;
Miao, Kou-Rong ;
Qiao, Chun ;
Zhuang, Yun ;
Shen, Wen-Yi ;
Hong, Ming ;
Fan, Lei ;
Liu, Peng ;
Xu, Wei ;
Li, Jian-Yong .
LEUKEMIA & LYMPHOMA, 2011, 52 (06) :1003-1009