Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

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reponame:Repositorio Institucional EdocUR

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Estrada Serrato, Carlos; Magíster en Ciencias con Énfasis en Genética Humana
Facultad de medicina; Universidad del Rosario
Butirilcolinesterasa humana (BChE); Cocaína; Gen BCHE; Polimorfismos de Nucleótido Simple (SNPs); Reacciones adversas; 610; Human Butyrylcholinesterase (BChE); BCHE gene; Cocaine; Single Nucleotide Polymorphisms (SNPs); Adverse reactions; Polimorfismos de Nucleótido Simple (SNPs; Genética
thesis / dissertation description
Human Butyrylcholinesterase (BChE; EC is a polymorphic enzyme synthesized in the liver and adipose tissue, widely distributed in the body and responsible for hydrolyze some choline esters such as procaine, aliphatic esters such as aspirin, drugs as methylprednisolone, mivacurium and succinylcholine and drug to use and abuse such as heroin and cocaine. It is coded by the BCHE gene (OMIM 147400), more than 100 variants have been identified, however not all of them have been studied fully, besides the most common form: usual or wild type. BCHE polymorphisms have been shown to produce enzymes with varying levels of catalytic activity. The molecular bases of some genetic variants of BCHE have been reported, such as the Atypical (A), fluoride-resistant 1 and 2 (F-1 and F2), silent (S), Kalow (K), James (J) and Hammersmith (H) variants. In this study, validated instrument Lifetime Severity Index for Cocaine Use Disorder (LSI-C) was applied to evaluate the severity of the consumption of "cocaine" throughout life. In addition, Single Nucleotide Polymorphisms (SNPs) were identified in the BCHE gene, responsible for adverse reactions in patients consumers of "cocaine" by gene sequencing and the effect of these SNPs on the function and structure of the protein was predicted, using bio-informatics tools. The LSI-C instrument provided results in four dimensions: consumption throughout life, recent use, psychological dependence and quit attempt of cocaine use. Molecular analysis studies allowed to observe two coding SNPs (cSNPs) in 27.3% of the sample, c.293A>G (p.Asp98Gly) and c.1699G>A (p.Ala567Thr), located in exons 2 and 4, which are, from the functional point of view, to the atypical variant (A) [dbSNP: rs1799807] and Kalow variant (K) [dbSNP: rs1803274] of BChE enzyme, respectively. In silico prediction established for SNPs p.Asp98Gly a pathogenic character, while for the SNPs p.Ala567Thr showed neutral behavior. The analysis of the results allows proposing the existence of a relationship between polymorphisms or genetic variants responsible for the low catalytic activity and/or low plasma concentration of BChE enzyme and some of the adverse reactions in cocaine consumer patients.