Polymorphisms of Thymidylate Synthase Enhancer Region (TSER) and Upstream Stimulatory Factor 1 (USF1 306G > A) Genes are Associated with Plasma Homocysteine Level and Susceptibility to Ischemic Stroke in a Korean Population

摘要

The thymidylate synthase enhancer region (TSEld gene promoter has a variable tandem repeat polymorphism containing an upstream stimulatory factor (USF) family E-box binding site that affects expression of the enzyme. Also, the tandem repeat polymorphism of the TS promoter is known to affect plasma homocysteine (phcy) level. Upstream stimulatory factor 1 (USFl) is a transcription factor controlling expression of several genes involved in lipid and glucose homeostasis. We therefore investigated the influence of the TSER and the USFl gene polymorphisms on sus-ceptibility to ischemic stroke and phcy levels in a Korean population. The TSER and USFl 306G > A genotypes in 234 ischemic stroke patients and 203 age and sex-matched controls subjects were identified by PGR. Plasma hey levels were measured by fluorescent polarizing immunoassay. Frequencies of USFl 306G > A genotypes and TSER variants were not significantly different between the controls and patients with ischemic stroke. The stroke patients, however, had significantly higher phcy levels with the TSER 2R3R+2R2R genotype than the control group. Also, phcy levels differed according to combined TSER and USFl 306G>A genotypes. The combined TSER 2R3R+2R2R and USFl 306GA+AA genotypes and the phcy concentration of the patient group were also higher than those of the control group (p = 0.027). In addition, the phcy concentration of the combined TSER 2R3R+2R2R and USFl 306AA genotype was higher than that of the combined TSER 3R3R and USFl 306GG genotype (p= 0.004) in the patient group. Our results suggest that TSER and USFl 306G>A polymorphisms may influence total homocysteine levels, leading to an increased risk of ischemic stroke.