Genetic variants in the enhancer region of the thymidylate synthase gene in the Chilean population

Aims Thymidylate synthase (TYMS) is an important target enzyme for the fluoropyrimidines. The TYMS gene enhancer region possesses tandemly repeated (TSER) sequences that are polymorphic in humans and different among ethnic groups. The aims of this study were to estimate the frequencies of the TSER variants in two hospital samples located in the northern (HSJ) and eastern (CLC) parts of Santiago, Chile, and compare them with the frequencies in other populations of different ethnic origin. Methods Genotyping of TSER variants in 368 Chilean subjects (HSJ = 178 and CLC = 190) by polymerase chain reaction; products of amplification were electrophoresed, obtaining fragments of 250 bp for allele TSER*3 and 220 bp for allele TSER*2. Results The two hospital samples had different degrees of Amerindian admixture (HSJ 34.5%; CLC 15.9%), which was not reflected in the observed frequencies of the CLC TSER*3: 56.8% and HSJ TSER*3: 53.4%. Conclusions Our results are unexpected, considering that genetic markers in the Chilean population generally show allele frequencies between those observed in European Caucasians and Amerindians and that the percentage of Amerindian admixture in CLC is lower than in HSJ. Both hospitals should have had greater frequencies of TSER*3 than were found and the frequency should have been greater in HSJ than in CLC; the only logical explanation of our results is that the frequency of this allele in aboriginal Chilean people is much lower than the 80% estimated for Mongoloid populations.