The influence of polymorphisms in the drug transporter, ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia.

Background: Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL.

Methods: Three single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs 3213619 T129C, rs 2032582 G2677T and rs1045642 C3435T) were analysed in 70 Saudi children with ALL and 60 control subjects.

Association Between NR3C1 Gene Polymorphisms and Toxicity Induced by Glucocorticoids Therapy in Saudi Children with Acute Lymphoblastic Leukemia.

Background: Glucocorticoids (GCs) are key hormones used for the treatment of acute lymphoblastic leukemia (ALL) in children, but their cytotoxic effects are not well defined. The aim of this study was to evaluate the association between polymorphisms in NR3C1 encoding for protein involved in the GCs metabolism and its role in the development of ALL and the toxicity outcome, in terms of liver toxicity, glucose abnormality and infections, in ALL Saudi children. Methods: The following polymorphisms BCII rs41423247, ER22/23 EK rs6189 and rs6190 and N363S rs6195 in NR3C1 were analyzed in 70 children with ALL treated according to the ALL 2000 study protocol in comparison to 60 control subjects.