ABCBl polymorphism

ABCBl is a 170-kDa integral membrane glycoprotein. It consists of 12 transmembrane helices and 2 nucleotide binding domains. There is no disease known that is linked to a nonfunctional protein due to mutations within the ABCBl gene, so far. In recent years, many screening studies with human individuals have been performed on the association of ABCBl polymorphisms with ABCBl expression and function in tissues and with the pharmacokinetics and pharmacodynamics of drugs [64]. However, still there are discrepancies in the results, and furthermore, no... 

The effect of CYP3A5 and MDRl (ABCBl) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 2004 14(3) 147-154. 

Brambila-Tapia, A.J.-L., 2013. MDRl (ABCBl) polymorphisms functional effects and clinical implications. Revista de Investigacidn Clinica, 65(5), pp. 445-454. 

Kurzawski M, Dabrowska J, Dziewanowski K, Domanski L, Peruzynska M, Drozdzik M (2014) CYP3A5 and CYP3A4, but not ABCBl polymorphisms affect tacrolimus dose-adjusted trough concentrations in kidney transplant recipients. Pharmacogenomics 15 179-188... 

Hawwa AF, McKieman PJ, Shields M, Millership JS, Collier McElnay JC. Influence of ABCBl polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant. Br J Clin Pharmacol 2009 68(3) 413-21. 

Keywords ABCBl ABCCl ABCC2 ABCG2 OATPIBI OATP1B3 polymorphisms transport. 

More than 50 polymorphisms, three insertions/deletions, and several promoter alterations that modify gene transcription have been described in the ABCBl gene. There are three single-nucleotide polymorphisms (SNPs) that are common in most racial populations and demonstrate strong linkage disequilibrium the synonymous... 

Table 4.2 Primers used to amplify selected polymorphisms in the ABCBl, ABCG2, OATPIBI, and OATP1B3 genes... 

Eichelbaum, M., Fromm, M. F., and Schwab, M. (2004) Clinical aspects of the MDRl (ABCBl) gene polymorphism. Ther. Drug Monit. 26, 180-185. 

Schaefer, M., Roots, 1., and Gerloff, T. (2005) In vitro transport characteristics discriminate wildtype mdrl (abcbl) from ala893ser and ala893thr polymorphisms. Eur. J. Clin. Pharmacol. 61,718. 

Meissner, K., Jedlitschky, G., Meyer zu Schwabedissen, H., et al. (2004) Modulation of multidrug resistance P-glycoprotein 1 (ABCBl) expression in human heart by hereditary polymorphisms. Pharmacogenetics. 14, 381-385. 

Genetic polymorphisms in the P-gp gene may be important in influencing the outcome of pharmacotherapy (58), and several SNPs in the ABCBl gene have been described. The three most mentioned SNPs are P-gp 6 (C3435T), 7 (G2677T/A), and 8 (C1236T). 

Mealey, K.L., Fidel, Gay, J.M., Imperllizeri, J.A., Clifford, C.A. and Bergman, P.J. (2008) ABCBl-1 Delta polymorphism can predict hematologic toxicity in dogs treated with vincristine. Journal of Veterinary Internal Medicine/ American College of Veterinary Internal Medicine, 22, 996-1000. 

Lapatinib had been shown ex vivo to be primarily metabolized by CYP3A4/5 with a minor contribution from CYP2C19, and to be a substrate of the transporters MDRl(ABCBl) and BCRP(ABCG2). A hypothesis was proposed whereby polymorphisms in these genes would be associated with a propensity to develop rash and/or diarrhea. 

Ozawa S, Soyama A, Saeki M, Fukushima-Uesaka H, Itoda M, Koyano S, Sai K, Ohno Y, Saito Y, Sawada J. Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3AS and MDRl/ABCBl. Drug Metab Pharmacokmet 2004 19(2) 83-95. 

A polymorphism of the ABCBl gene may be associated with a risk of tacrohmus-induced neurotoxicity after liver transplantation. In six patients with neurotoxicity and 11 without neurotoxicity, high tacrolimus concentration, liver dysfunction, and a mutation in position 2677 in exon 21 were positive predictive factors for tacrolimus-induced neurotoxicity (37). 

Yamauchi A, leiri I, Kataoka Y, Tanabe M, Nishizaki T, Oishi R, Higuchi S, Otsubo K, Sugimachi K. Neurotoxicity induced by tacrolimus after hver transplantation relation to genetic polymorphisms of the ABCBl (MDRl) gene. Transplantation 2002 74(4) 571-2. 

Choudhuri, S. and Klaassen, C.D. (2006) Structure, function, expression, genomic organization, and single nucleotide polymorphisms ofhuman ABCBl (MDRl), ABCC (MRP), and ABCG2 (BCRP) effiux transporters. International Journal of Toxicology, 25, 231-259. 

Pauli-Magnus C, Kroetz DL, Functional implications of genetic polymorphisms in the multidrug resistance gene MDRl (ABCBl),... 

Siddiqui A, Kerb R, Weale M E, et al. (2003). Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCBl. N. Engl. J. Med. 348 1442-1448. 

Genetic polymorphisms in ABCBl and ABCg2 may be important also in influencing the pharmacokinetics of irinotecan and its metabolites (see above). 

Lepper E R, Nooter K, Verweij J, et al. (2005). Mechanism of resistance to anticancer drngs The role of the polymorphic ABS transporters ABCBl and ABCG2. Pharma-cogenom. 6 115-138. 

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