Splicing variant profiles and single nucleotide polymorphisms of the glucocorticoid receptor gene in relation to glucocorticoid sensitivity of B-cell precursor acute lymphoblastic leukaemia

2017 ◽  
Vol 36 (1) ◽  
pp. 245-251 ◽  
Author(s):  
Meixian Huang ◽  
Takeshi Inukai ◽  
Keiko Kagami ◽  
Masako Abe ◽  
Tamao Shinohara ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Acute Lymphoblastic Leukaemia ◽  
B Cell ◽  
Lymphoblastic Leukaemia ◽  
Receptor Gene ◽  
Nucleotide Polymorphisms ◽  
Cell Precursor ◽  
Single Nucleotide ◽  
Splicing Variant ◽  
Glucocorticoid Receptor Gene

scholarly journals Significance of TPMT and NUDT15 variants in 6-mercaptopurine metabolism in acute lymphoblastic leukaemia/lymphoma patients

2021 ◽  
Vol 66 (2) ◽  
pp. 253-262
Author(s):  
E. S. Kotova ◽  
O. A. Gavrilina ◽  
A. B. Sudarikov
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Adverse Reactions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Functional Variant ◽  
Metabolism Enzyme ◽  
Key Steps

Introduction. Among main curative substances in acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is 6-mercaptopurine (6-MP). However, the severity of adverse reactions (ADRs) to this drug varies considerably among patients, which is sometimes conditioned by individual single nucleotide polymorphisms in key 6-MP metabolism enzyme genes.Aim — a literature review on the role of TPMT and NUDT15 gene variants in 6-MP metabolism in ALL/LBL.Main findings. The TPMT and NUDT15 genes encode enzymes mediating key steps of the 6-MP metabolism. The metabolites determine the 6-MP therapeutic and toxic properties, with ADRs emerging when their concentrations alter. A number of TPMT and NUDT15 single nucleotide polymorphisms are associated with varied activities of the encoded enzymes, and their allelic combinations condition functional and non-functional phenotypes. Non-functional variant carriers more likely develop toxicity on 6-MP treatment compared to functional phenotypes. Non-functional TPMT/NUDT15 carriers should have the 6-MP dosage reduced to minimise emerging ADRs.

Histamine H3 receptor gene variants associated with drug abuse in patients with cocaine use disorder

2020 ◽  
Vol 34 (11) ◽  
pp. 1326-1330
Author(s):  
Iñigo Pallardo-Fernández ◽  
José Ramón Muñoz-Rodríguez ◽  
Carmen González-Martín ◽  
Luis F Alguacil
Keyword(s):  
Drug Abuse ◽  
Single Nucleotide Polymorphisms ◽  
Receptor Gene ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Histamine H3 Receptor ◽  
Cocaine Use ◽  
H3 Receptor ◽  
Histamine H3

Background: Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. Aims: We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. Methods: Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. Results: The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. Conclusions: The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

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