Hyperhomocysteinemia as an Independent Risk Factor for Silent Brain Infarction: Inverse Correlation with Folate in Patients with MTHFR 677TT Genotype

ABSTRACT

BACKGROUND: Silent brain infarction (SBI) are common in elderly people and are associated with an increased risk of clinically apparent stroke. Hyperhomocysteinemia is also an independent risk factor for ischemic stroke. This study was undertaken to determine whether hyperhomocysteinemia was associated with SBI, and also to find prevention against SBI through correlation among homocysteine, folate, and vitamin B12. METHODS: We enrolled 103 SBI patients and 107 healthy individuals and checked their fasting plasma homocysteine levels and analyzed the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. RESULTS: The plasma homocysteine levels in subjects with SBI (12.91 +/- 5.84 micromoll/L) were significantly higher than those in subjects without SBI (10.21+/-3.92 micromol/L; p or =13.3 micromol/L), moderate (10.0 to 13.2 micromol/L), and low (< or =9.9 micromol/L) groups, the adjusted odds ratio (AOR) for SBI was significantly greater in subjects with high group compared with in subjects with low group (AOR, 3.58; 95% CI, 1.69 to 7.58 p = 0.0009). When we combined each MTHFR genotype with SBI patients and controls, the plasma homocysteine concentrations showed a significant inverse correlation with folate only in SBI patient with MTHFR 677 TT genotype (correlation coefficient -0.495; p = 0.023). CONCLUSIONS: Hyperhomocysteinemia is an independent risk factor for SBI. Our findings show that reducing plasma hommocysteine level by folate intake may prevent SBI in patients with homozygous C677T mutation in the MTHFR gene.