Byung-Ok Choi, M.D., Yong Seong Kim, Ph.D.*, Ok-Joon Kim, M.D., Jung-Ho Seo, M.D., Nam-Keun Kim, Ph.D.

Transcription

1 Hyperhomocysteinemia as an Independent Risk Factor for Silent Brain Infarction - Inverse Correlation with Folate in Patients with MTHFR 677TT Genotype - Byung-Ok Choi, M.D., Yong Seong Kim, Ph.D.*, Ok-Joon Kim, M.D., Jung-Ho Seo, M.D., Nam-Keun Kim, Ph.D. Department of Neurology, College of Medicine, Ewha Womans University Department of Neurology, and Institute for Clinical Research College of Medicine, Pochon CHA University, Department of Chemistry, Kyungnam University* 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 ( mol/l) were significantly higher than those in subjects without SBI ( mol/l; p < ). When plasma homocysteine levels were stratified into high (13.3 mol/l), moderate (10.0 to 13.2 mol/l), and low (9.9 mol/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 = ). 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: ; 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. J Korean Neurol Assoc 21(2):134~140, 2003 Key Words : Silent brain infarction, Homocysteine, Folate, MTHFR, Risk factor Byung-Ok Choi, M.D. 134 Copyright 2003 by the Korean Neurological Association

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3 Table 1. Baseline characteristics in patients with silent brain infarction and control subjects Controls Silent brain infarction (n = 107) (n = 103) COR 95% CI p* Clinical Age (mean SD) Female (ratio) 57 (53.3%) 56 (54.4%) Hypertension 44 (41.1%) 68 (66.0%) DM 16 (15.0%) 20 (19.4%) Blood biochemistry Homocysteine < Folate Vitamine B Total cholesterol Triglyceride HDL-Cholesterol LDL-Cholesterol BUN Creatinine HbA1C COR; crude odds ratio, 95% CI; 95% confidence intervals, * Chi-square test for the categorical data, and two-sample t-test for the continuous data. 136 J Korean Neurol Assoc / Volume 21 / April, 2003

4 Figure. 1. Localization of silent brain infarcts on brain MRI. Table 2. The odds ratio of MTHFR genotypes between patients with silent brain infarction and control subjects MTHFR (%) Controls Silent brain infarction (n = 107) (n = 103) genotype 677 CC 29 (27.1) 26 (25.2) 677 CT 61 (57.0) 56 (54.4) 677 TT 17 (15.9) 21 (20.4) T allele ratio CC vs CT COR (95% CI) ( ) AOR (95% CI) ( ) CC vs TT COR (95% CI) ( ) AOR (95% CI) ( ) CC vs CT + TT COR (95% CI) ( ) AOR (95% CI) ( ) COR (95% CI); crude odds ratio and 95% confidence intervals, AOR (95% CI); adjusted odds ratio and 95% confidence intervals, adjusted for age, sex, hypertension and diabetes mellitus MTHFR; methylenetetrahydrofolate reductase J Korean Neurol Assoc / Volume 21 / April,

5 Table 3. Relative risks of the patients with silent brain infarction according to tertile of plasma homocysteine levels Homocysteine COR (95% CI) AOR (95% CI) 9.9 mol/l mol/l 2.33 ( ) 3.07 ( ) 13.3 mol/l 3.99 ( ) 3.58 ( ) p < < COR (95% CI); crude odds ratio and 95% confidence intervals, AOR (95% CI); adjusted odds ratio and 95% confidence intervals, adjusted for age, sex, hypertension and diabetes mellitus Table 4. Correlation between homocysteine and folate levels in patients with silent brain infarction and control subjects among MTHFR polymorphism MTHFR Controls Silent brain infarction (n = 107) (n = 103) 677CC homocysteine folate coefficient p CT homocysteine folate coefficient p TT homocysteine folate coefficient p coefficient; correlation coefficient with using the correlation analysis MTHFR; methylenetetrahydrofolate reductase 138 J Korean Neurol Assoc / Volume 21 / April, 2003

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