Document Details

Document Type : Thesis 
Document Title :
MDR1 AND NR3C1 GENES POLYMORPHISMS AFFECT THE OUTCOME AND TOXICITY OF GLUCOCORTICOID IN SAUDI CHILDREN ACUTE LYMPHOBLASTIC LEUKEMIA
الأشكال الجينية تؤثر على النتيجة و سيمة الإستيرويد في سرطان الدم اللمفاوي الحاد عند الأطفال السعوديين.
 
Subject : Faculty of Applied Medical Sciences 
Document Language : Arabic 
Abstract : Background: Glucocorticoids (GCs) play an essential role in the treatment of childhood acute lymphoblastic leukemia (ALL) in Saudi Arabia, but treatment with these agents overwhelmingly results in several severe side effects due to gene polymorphisms. This study is the first survey of its kind in Saudi children. The aim of this study was to evaluate the association between polymorphisms of genes multidrug resistance 1 (MDR1, ABCB1, P-gp) and glucocorticoid receptor (GR, NR3C1) encoding for protein involved in the pharmacokinetics /pharmacodynamics of these drugs and the appearance of side effects, particularly infections, in a small population of ALL Saudi children. Methods: Polymorphisms of NR3C1 and MDR1 genes were analyzed in 70 Saudi children with ALL, treated according to the ALL 2000 study protocol. Toxicities were assessed and their association with genotypes was evaluated according to Common Toxicity Criteria (NCI-CTC). Results: Significant association (p ≤ 0.009) between the polymorphism of N363S (NR3C1 gene) and the occurrence of glucose metabolism abnormalities in ALL patients’ carriers of genotype AG, showing an increase of 40% in the risk to develop glucose abnormality when treated with GC. Also found the polymorphism C3435T (ABCB1) (TT, CT) genotype had an incidence of infection toxicity (p=0.05) more than CC genotype. Conclusion: This study suggests that the polymorphism in N363S is more sensitive to glucocorticoids and it may contribute to the glucose abnormality for these patients. Regarding the incidence of infection toxicity, the polymorphism of the C3435T (ABCB1 gene), may contribute to potential life-threatening infection toxicity. 
Supervisor : Dr. Talaat Mirza 
Thesis Type : Master Thesis 
Publishing Year : 1439 AH
2018 AD 
Co-Supervisor : Dr. Refaat Al-Fayoumi 
Added Date : Wednesday, May 2, 2018 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
ابتسام محمد الهنديAlhindi, Ebtisam MohammedResearcherMaster 

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