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

The thymidylate synthase enhancer region (TSER) 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 (USF1) 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 USF1 gene polymorphisms on susceptibility to ischemic stroke and phcy levels in a Korean population. The TSER and USF1 306G >A genotypes in 234 ischemic stroke patients and 203 age and sex-matched controls subjects were identified by PCR. Plasma hey levels were measured by fluorescent polarizing immunoassay. Frequencies of USF1 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 USF1 306G >A genotypes. The combined TSER 2R3R+2R2R and USF1 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 USF1 306AA genotype was higher than that of the combined TSER 3R3R and USF1 306GG genotype (p = 0.004) in the patient group. Our results suggest that TSER and USF1 306G >A polymorphisms may influence total homocysteine levels, leading to an increased risk of ischemic stroke.