Methylenetetrahydrofolate Reductase Gene Single Nucleotide Polymorphism in Korean Population with Ischemic Stroke

Kim, In Gyu; Kim, Joon Tae; Kim, Myeong Kyu

Abstract

The identification of novel markers of stroke risk is of key importance, both for risk prediction and potential modification to reduce future events. Recently, a mutation (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene was identified to cause elevation of the plasma homocysteine level that is associated with increased risk of vascular disorders. The authors aimed to elucidate the genetic contribution of MTHFR C677T single nucleotide polymorphism (SNP) to ischemic stroke in Korean population. A total of 332 individuals with ischemic stroke and 110 controls without any evidence of having brain lesion were enrolled. To assess the risk of ischemic stroke, clinical characteristics and MTHFR C677T genotypes of all participants were compared. Genotyping of MTHFR C677T SNP was performed for each individual using PCR amplification and direct sequencing in both strands. The frequency of the mutant heterozygote (677CT) and homozygote for C677T SNP in control subjects were 55.5 and 13.6%, respectively. The mean plasma homocysteine level was significantly higher (p<0.001) in ischemic stroke patients group (11.4+/-4.6 micronmol/L) than in control group (9.4+/-3.3micronmol/L). Also, the plasma homocysteine levels were significantly increased with the 677T allele in a dose-dependent manner (p<0.001). Despite the clear association between MTHFR C677T genotypes and elevated homocysteine level, no definite association between MTHFR C677T genotypes and ischemic stroke was evident in Korean population. Elevated plasma homocysteine level is associated with increased risk of ischemic stroke and MTHFR 677T allele may be an independent risk factor for elevated plasma homocysteine level in Korean population.