Related Experiment Videos
Methylenetetrahydrofolate reductase gene polymorphism and ischemic stroke in Japanese
H Morita1, H Kurihara, S Tsubaki
1Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Japan.
Insights
The V allele of the MTHFR gene is linked to a higher risk of ischemic stroke in elderly Japanese individuals. This genetic link may increase stroke risk by raising homocysteine levels, suggesting folate supplementation could be beneficial.
Area of Science:
- Genetics
- Neurology
- Cardiovascular Medicine
Background:
- Hyperhomocysteinemia is an independent risk factor for atherosclerotic and thromboembolic diseases.
- The alanine/valine (A/V) gene polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme affects homocysteine metabolism.
- The VV genotype of MTHFR is associated with reduced enzyme activity and elevated plasma homocysteine levels.
Purpose of the Study:
- To investigate the association between the V allele of the MTHFR gene and ischemic stroke in an elderly Japanese population.
- To determine if MTHFR genotype influences plasma homocysteine levels in relation to stroke risk.
Main Methods:
- Case-control study involving 256 stroke patients and 325 control subjects.
- Diagnosis of cerebral infarction confirmed by CT scan.
- MTHFR genotyping performed using polymerase chain reaction and HinfI digestion.
Main Results:
- The V allele frequency was significantly higher in stroke patients (0.45) compared to controls (0.32).
- Odds ratios for ischemic stroke were 1.51 for AV genotype and 3.35 for VV genotype compared to AA genotype (P=0.041 and P<0.001, respectively).
- Plasma homocysteine levels were significantly higher in individuals with the VV genotype, particularly those with low folate levels.
Conclusions:
- The V allele of the MTHFR gene is significantly associated with cerebral infarction in the elderly Japanese population.
- The VV genotype may increase ischemic stroke risk by predisposing individuals to higher plasma homocysteine levels.
- Dietary folate supplementation may offer benefits, especially for individuals with the VV genotype.
Abstract:
Hyperhomocyst(e)inemia has been identified as an independent risk factor for atherosclerotic and thromboembolic diseases such as coronary artery disease, cerebral artery disease, and venous thrombosis. Recently, the alanine/valine (A/V) gene polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes that catalyzes the remethylation of homocysteine, was reported. The VV genotype is correlated with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the association between the V allele of the MTHFR gene and ischemic stroke in an elderly Japanese population. The diagnosis of cerebral infarction of all study patients was confirmed by CT of the brain. The MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. In 256 stroke patients and 325 control subjects, the frequencies of the V allele were 0.45 and 0.32, respectively. The odds ratios and 95% confidence intervals adjusted for the other risk factors were, respectively, 1.51 (1.02 to 2.23) for the AV genotype and 3.35 (1.94 to 5.77) for the VV genotype compared with the AA genotype. Both of these effects were statistically significant (P=0.041 and P<0.001, respectively). In patients with multiple infarcts in particular, the allele frequency of the V mutation was 0.56, and the association between the V allele and stroke was highly significant. Plasma homocyst(e)ine levels were significantly higher in patients with the VV genotype than in patients with the AA or AV genotype, especially those with low plasma folate levels. The V allele of the MTHFR gene was significantly associated with cerebral infarction in an elderly Japanese population in a codominant manner. The VV genotype may contribute to risk for ischemic stroke through a predisposition to increased plasma homocyst(e)ine levels, and dietary folate supplementation may be of benefit, particularly to patients with this genotype.