Abstract

VILLEGAS MENDOZA, Cecilia Andreina et al. Thymidylate synthase gen polymorphism 1494del6 in a population from the central region of Venezuela. Acta bioquím. clín. latinoam. [online]. 2015, vol.49, n.3, pp.321-327. ISSN 0325-2957.

Thymidylate synthase enzyme (TS) codified by the TYMS gene is inhibited by chemotherapeutic agents such as 5-Fluoruacil (5-FU) and Methotrexate (MTX). Several studies have postulated the existence of an inverse relationship between enzyme levels and 5-FU and MTX therapeutic benefits. In the TYMS gene, there are polymorphisms associated with the TS expression, one of them consisting of an insertion (+6pb) or deletion (-6pb) of 6 bp at position 1494 in the 3’UTR region (1494del6); the deletion is associated with low levels of enzyme. The aim of this work was to determine the 1494del6 polymorphism of the TYMS gene in a sample of 260 no-consanguineous healthy individuals from the Central region of Venezuela. Informed consent was obtained and a blood sample was taken to isolate DNA and to amplify a sequence of 142/148 pb by PCR. The PCR product was digested with Dra I enzyme, the restriction patterns were checked by electrophoresis on 8% polyacrylamide gel, and genotypes were determined and compared with those obtained in other populations. Three genotypes were found, whose frequencies were: -6pb/-6pb (15,8%), +6pb/-6pb (45,4%) and +6pb/+6pb (38,8%), the latter being associated with deficient response to treatment with 5-FU and MTX. This research is an initial step in generating data of pharmacogenetics importance with reference to TYMS gene in a Venezuelan population.

Keywords : Thymidylate synthase; TYMS Polymorphism 3’ UTR; 1494del6; Pharmacogenetics; Venezuela.