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Title: CYP3A5, Tacrolimus and kidney transplantation
Authors: Sadek, Zahraa
Advisors: Chalhoub, Elias
Subjects: Transplantation immunology
Issue Date: 2016
Introduction: Tacrolimus is an immunosuppressive agent belonging to the calcineurin inhibitor group that has emerged as an important therapeutic alternative to cyclosporine following organ transplantation. Its use is highly efficient at preventing rejection in heart, pancreas, bone marrow, lung, liver, and kidney transplantation. Once absorbed, this drug is mainly metabolized and inactivated in the cells by two enzymes of the cytochrome P450 family, CYP3A4 and CYP3A5. Studies showed the presence of a SNP in intron 3 of the gene coding for CYP3A5 where there is a A6986G transition at position rs776746. This substitution leads to a decrease in the activity of CYP3A5. Experimental procedure: the purpose of this study is to give an idea about the frequency of the SNP in the Lebanese population, to compare it with the frequency in the Caucasian population, and to establish a correlation between this SNP and Tacrolimus metabolism based on Tacrolimus concentration in blood, taking into consideration weight and hemoglobin levels. 68 blood samples were collected from SGHUMC and Saint George laboratories. DNA was extracted from these samples, and genotyping for the CYP3A5 gene was performed using PCR-RFLP method. Statistical analysis was performed to study the correlation between the genotypes and Tacrolimus metabolism. Results: The results showed that the frequency of the A/A genotype was 1.5% (n=1), that of A/G genotype was 7.4% (n= 5) and that of G/G genotype was 91.2% (n= 62). Analysis of Tacrolimus concentrations and daily doses didn't show any significant difference between patients of different genotype groups. Statistical analysis showed that Hemoglobin could be a possible confounders affecting blood Tacrolimus concentrations. Conclusion: The frequency of the mutant alleles in the Lebanese population is similar as in Caucasian population. The A6986G SNP in intron 3 of CYP3A5 gene didnt have any influence on Tacrolimus metabolism or its concentration in blood.
Includes bibliographical references (p. 84-87).

Supervised by Dr. Elias Chalhoub.
Rights: This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder
Ezproxy URL: Link to full text
Type: Thesis
Appears in Collections:UOB Theses and Projects

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