Identificación de polimorfismos en el gen DPYD en pacientes con toxicidad grave a fluoropirimidinas

Kaczmarczyk, Bartosz (2019). Identificación de polimorfismos en el gen DPYD en pacientes con toxicidad grave a fluoropirimidinas. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Identificación de polimorfismos en el gen DPYD en pacientes con toxicidad grave a fluoropirimidinas
Author/s:
  • Kaczmarczyk, Bartosz
Contributor/s:
  • López Fernández, Luis Andrés
  • Miedes Vicente, Eva
Item Type: Final Project
Degree: Grado en Biotecnología
Date: June 2019
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

Full text

[img] PDF - Users in campus UPM only - Requires a PDF viewer, such as GSview, Xpdf or Adobe Acrobat Reader
Download (2MB)

Abstract

Pharmacogenetics is the study of variations in DNA sequence as related to drug response. DPYD gene is a popular target in pharmacogenetic research. It codes for Dihydropyrimidine dehydrogenase (DPD), a key enzime in fluoropyrimidines, 5- fluorouracil and its prodrug capecitabine, catabolic pathway. Fluoropyrimidines are chemotherapeutical drugs commonly used in colorectal cancer treatment. Variations in DPYD are strongly related to the ocurrence of severe adverse effects. There are only four polymorphisms validated for clinical practice that cause a deficency in the enzimatic activity. Many of the patients do not present any of those variants and suffer severe toxicities during treatment. There are some common variants which effect is still in doubt and to define their impact is important. Also, some patients are carriers of rare or even unique mutations that are not analyzed in pharmacogenetic common tests and cause adverse effects. The aims of this study are to investigate the relation between a fairly common polymorphism, c.2194G>A, and the risk of suffering severe toxicities; to assess the inclusion of a validated deep intronic variant, c.1129-5923C>G, in the test performed in the Pharmacogenetics Laboratory in Hospital General Universitario Gregorio Marañón; and to analyze the exon sequences of patients who have experienced severe adverse effects and does not present any of the validated polymorphisms, accompanied with phenotype and in silico analysis. Even though a statistical evidence could not be found between c.2194G>A and severe toxicities, it can be suggested to keep studying this association. Two patients of the 102 genotyped were found to be carriers of c.1129-5923C>G variant and both suffered severe adverse effects. It could be useful to consider the inclusion of this variant in the pharmacogenetic test. In the exon sequencing analysis, a rare variant, c.257C>T, and three mutations not described previously have been found: c.86G>A, c.1084G>A and c.2324T>G, all of them, but particulary the last one, could be causative of toxicities.

More information

Item ID: 57509
DC Identifier: http://oa.upm.es/57509/
OAI Identifier: oai:oa.upm.es:57509
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 16 Dec 2019 05:56
Last Modified: 16 Dec 2019 05:56
  • Logo InvestigaM (UPM)
  • Logo GEOUP4
  • Logo Open Access
  • Open Access
  • Logo Sherpa/Romeo
    Check whether the anglo-saxon journal in which you have published an article allows you to also publish it under open access.
  • Logo Dulcinea
    Check whether the spanish journal in which you have published an article allows you to also publish it under open access.
  • Logo de Recolecta
  • Logo del Observatorio I+D+i UPM
  • Logo de OpenCourseWare UPM