MTHFR A1298C Gene Polymorphism: Independent Risk Factor for Ischemic Stroke?

Kim, Nam Keun; Choi, Byung Ok

Abstract

BACKGROUND
A genetic aberration in the MTHFR gene has been shown to result in reduced MTHFR enzyme activity and induced hyperhomocysteinemia. Recently, a second genetic polymorphism in MTHFR at position 1298 was reported. However, the association between the A1298C MTHFR polymorphism and ischemic stroke has not been reported. Therefore, we attempted to determine whether the MTHFR C677T and A1298C gene polymorphisms were associated with ischemic stroke. METHODS: We enrolled 220 ischemic stroke patients and 203 healthy individuals and compared their fasting plasma homocysteine levels and analyzed the MTHFR C677T and A1298C polymorphisms. RESULTS: Plasma homocysteine levels were significantly higher (p<0.05) in ischemic stroke patients (10.86 +/- 5.07 micro mol/L) than in control subjects (9.39 +/- 2.98 micro mol/L). Despite a clear association between 677TT genotype and elevated homocysteine level, there was no association between MTHFR C677T polymorphism and ischemic stroke. On the other hand, the odds ratio and 95% CI adjusted for other risk factors were 1.80 (1.08 to 3.00) for the 1298AC genotype, and 8.98 (1.00 to 80.42) for the 1298CC genotype. The adjusted odds ratio (AOR) for the 1298AC/CC genotypes were also significantly higher than that in the controls (AOR, 1.96; 95% CI, 1.19 to 3.24). However, in the analysis of combined genotypes with C677T and A1298C polymorphism, the AOR was not statistically significant. CONCLUSIONS: MTHFR A1298C gene polymorphism may be an independent risk factor for ischemic stroke. Our findings suggest that prediction of ischemic stroke may be possible by analyzing genetic defects.