Document Details

Document Type : Thesis 
Document Title :
INCREASE RISK OF ACUTE LEUKEMIA DUE TO POLYMORPHISM OF CYP3A4 AND CYP3A5 DETOXIFICATION ENZYME.
زيادة خطر احتمال الإصابة بسرطان الدم الحاد بسبب تعدد أشكال إنزيمي CYP3A4 و CYP3A5.
 
Subject : Faculty of Applied Medical Sciences 
Document Language : Arabic 
Abstract : Background: CYP3As are microsomal enzymes responsible for the oxidative metabolism of used drugs. They induce naturally occurring and synthetic glucocorticoids e.g. dexamethasone, pregnenolone, and the macrolide antibiotic, rifampicin. Glucocorticoids play important roles in acute lymphoblastic leukaemia treatment and are considered key for the treatment of children with ALL, particularly during initial phases. However, glucocorticoid therapy predominantly results in numerous and severe side effects. Inter-individual variation in steroid metabolising enzyme pathways, modified by individual somatic mutation, have been shown to affect drug responses and side effect severity. Methods: Two single nucleotide polymorphisms (SNPs) of the CYP3A gene (rs2740574 CYP3A4A and rs 776746 CYP3A5) were analysed in 70 Saudi children, treated according to the acute lymphoblastic leukaemia 2000 study protocol. 60 control subjects were also used. Treatment toxicities and their associations with genotypes were assessed and evaluated according to Common Toxicity Criteria. Results: Forty-five of 70 patients (64.29 %) were found to carry a mutated homozygous genotype of the CYP3A5*3 polymorphism. Statistical analyses using Pearson Chi-square 2 sided tests, showed a significant difference between ALL patients and control subjects (P = 0.044). This result was confirmed by the Fisher exact test (2 sided) (P = 0.052) (OR = 1.873; 0.998–1.901). CYP3A5*3 carriers also showed a significant incidence of liver toxicity (P = 0.039) (OR = 2.129; 1.648–2.751). The risk of infection incidence was increased to approximately 2.5 times that of patients with CYP3A5*3 polymorphisms (homozygous and heterozygous) (P = 0.053) (OR = 2.605; 1.318-5.149). Conclusion: This study suggests that polymorphisms in CYP3A5*3 may be associated with the development of ALL in children. In terms of liver toxicity and infection incidence, polymorphism CYP3A5*3 may contribute to potential life-threatening toxicity during paediatric ALL therapy, through glucocorticoid therapy. 
Supervisor : Prof. Refaat Alfayoumi 
Thesis Type : Master Thesis 
Publishing Year : 1441 AH
2019 AD 
Added Date : Sunday, November 24, 2019 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
عهود صالح المالكيAlmalki, Ohood SalehResearcherMaster 

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