Genetic Polymorphism of Thymidylate Synthase Enhancer Region (TSER) in Patients with Silent Brain Infarction

ABSTRACT

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for silent brain infarction (SBI). The plasma homocysteine (pHcy) level is influenced by the activities of enzymes such as 5,10-methylenetetrahydrofolate reductase (MTHFR). Thymidylate synthase (TS) also competes with MTHFR for their common cofactor, 5,10-methylenetetrahydrofolate (5,10-meTHF). The polymorphism of thymidylate synthase enhancer region (TSER) might affect homocystein metabolism by modulating the activity of TS, and may be a determinant of SBI by elevating pHcy concentrations. Therefore, we studied the polymorphism of TSER in patients with SBI. METHODS: 98 patients with SBI and 92 healthy controls were included in the study. The genotypes of TSER and MTHFR were identified with the PCR-RFLP methods. RESULTS: The mean pHcy level was significantly higher in SBI patients (13.5+/-8.5 micro mol/L) than in controls (10.3+/-4.1 micro mol/L)(p<0.01). The frequencies of MTHFR C677T genotype and TSER 28 bp tandem repeat genotype were not different between the patients and the controls. The pHcy concentrations were not considerably different between the 3R3R and 2R3R genotypes in the population as a whole (p=0.712), nor in subsets of patients with SBI (p=0.484). However, in cases with the TSER 3R3R genotype, the pHcy level was significantly higher in patients (14.0+/-10.26 micro mol/L) than in controls (9.9+/-3.1 micro mol/L)(p=0.006). Folate and pHcy was inversely correlated in the SBI patients with the TSER 3R3R genotype (r=-0.424, p=0.039). CONCLUSIONS: Our findings suggest that the TSER genotype is not a major determinant of pHcy concentrations and is neither a risk factor for SBI in the Korean population. However, further study will be needed to confirm this findings.