ANALYSIS OF THE TSER AND G > C VARIANTS IN THE TYMS GENE: A HIGH FREQUENCY OF LOW EXPRESSION GENOTYPES PREDICTED IN THE MEXICAN POPULATION.

Background. In the TYMS gene promoter, there is a repeat polymorphism (TSER) that affects the expression level of the thymidylate synthetase (TS) enzyme involved in the response to some anticancer drugs. The G > C transversion located in the TSER*3R allele decreases the expression level of the TS enzyme avoiding the upstream stimulatory factor (USF-1) binding site. Despite the biomedical impact of the SNP G > C, only TSER has been reported in most worldwide populations. Thus, we studied both TSER and SNP G > C variants in the Mexican population. Subjects and methods: A population sample (n= 156) was genotyped for the TSER and G > C variants by PCR and PCR-RFLPs, respectively, followed by PAGE and silver staining. Results : For TSER, the most frequent allele was 2R (52.56%), as well as the genotype 2R/3R (42.3%). Comparison with Latin American, European, and American (USA) populations suggest a heterogeneous worldwide distribution ( F ST -value  = 0.01564; p-value  = 0.0000). When the G > C variant was included (2RG, 3RG, and 3RC), a high frequency of low expression genotypes was observed: 2RG/2RG, 2RG/3RC, and 3RC/3RC (84.6%). Conclusion: The high frequency of genotypes associated with low TS enzyme expression justifies obtaining the TYMS gene variant profile in Mexican patient's candidates to pharmaceutical treatments like 5´-Fluoracil, methotrexate, and pemetrex.