Genetic polymorphism of thymidylate synthase enhancer region (TSER) in Korean

Thymidylate synthase (TS) regulates the production of DNA synthesis precursors and is an important target of cancer chemotherapy. The tandem-repeated 28-bp sequence in the 5'-terminal enhancer region of human thymidylate synthase has been reported to be polymorphic in different populations. We surveyed the genotype and allele frequency of thymidylate synthase enhancer region (TSER) in 474 Korean subjects. The genotypes and allele frequencies of TSER in the Koreans were compared with those in the other ethnic groups. Amplified fragments were separated by electrophoresis in 3.5% agarose gel. All four alleles of the repeat type (2, 3, 4 and 5) were confirmed by DNA sequencing. The frequencies of the TSER allele 2 and 3 (2R and 3R) were 18.47 and 80.8%, respectively. Six genotypes (2R2R, 2R3R, 3R3R, 2R5R, 3R4R, 3R5R) were identified. Among them, MR, 2R3R, 3R3R were the predominant ones (3.38%, 29.75%, 65.4%, respectively). The 4R allele was found at a lower allele frequency in the Korean population (0.21%) than in the African populations (2 to 7%). Interestingly, the 5R allele was found only in Eastern Asian populations such as Korean (0.53%), Chinese (0.18%) and Japanese (1.3%). Our results demonstrate significant ethnic variation in a TSER which may have significant impact on pyrimidine homeostasis and chemotherapy.