Beta
41244

Effect of multidrug resistance-1 gene polymorphisms on response to cyclosporine in renal transplanted patients

Thesis

Last updated: 06 Feb 2023

Subjects

-

Tags

Pharmacology

Advisors

Zaki, Magda M. , Abdel-Shafi, Sanaa , El-Shabouni, Tareq H. , Saber, Maha M.

Authors

Muhammad, Gumaa Mussttafa

Accessioned

2017-07-12 06:40:13

Available

2017-07-12 06:40:13

type

M.D. Thesis

Abstract

The aim of the present work is to study the pharmacogenomics in renal transplantedpatients receiving Cyclosporine A through assessing the effect of MDR-1 genepolymorphism namely at exon 26 (C3435T) and exon 11 (G1199A) on the pharmacokineticsof the drug. To reach this goal, we studied 40 recent renal transplanted patients receivingcyclosporine (26 males (65%) and 14 females (35%), Mean age = 27.5 years, range: 17-56years) recruited from King Fahd Unit of Cairo University. All patients are followed for atleast 3 months after renal transplantation by taking venous blood samples at fixed timesduring the whole period (after one week, one and three months). Each time, blood samplewas taken before (C0) and 2 hours after (C2) cyclosporine administration. Cyclosporine bloodconcentrations were determined in these samples by homogeneous enzyme immunoassay.For each patient DNA was extracted to study gene polymorphism by using the specificprimers for restriction fragment length polymorphism (RFLP)-technique, polymerase chainreaction followed by restriction enzyme. Out of 40 patients included in the study assessed forMDR-1 genotyping, G1199A mutation on exon 11 was the most frequent 77.5 % (31 pts)while there were only 22.5% (9 pts) wild type. Whereas patients at exon 26 with C3435Twild type were 60% (24 pts) while mutant type were 40% (16 pts). Patients carrying mutantG1199A responded better to cyclosporine compared to wild type, while patients with wildC3435T gave better response than that of mutant type.Pharmacogenetic aims for understanding how genetic variation contributes to variation inresponse to drugs. Studying polymorphisms affecting cyclosporine absorption can accountfor variability in response detected in renal transplanted patients.

Issued

1 Jan 2012

DOI

http://dx.doi.org/10.21473/iknito-space/35181

Details

Type

Thesis

Created At

05 Feb 2023