[Stroke and the genetics of hyperhomocysteinemia]

The T allele of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been shown to be a risk factor for stroke. Previous meta-analyses have shown that the individuals with the TT genotype have 1.26-1.37 times the risk for stroke as compared to those with the CC genotype. We performed a meta-analysis of all 5 Japanese studies that investigated the relationship between the MTHFR 677T allele and stroke. The risk of stroke was found to increase in a dose-dependent manner (OR for CT genotype: 1.35, 95% CI; 1.07-1.31, OR for TT genotype: 2.05, 95%CI; 1.51-2.78). This estimate was almost twice as high as those reported from Europe, suggesting that Japanese individuals may be more susceptible to stroke related to the MTHFR 677T allele, although this may be due to publication biases. Two studies have reported that the MTHFR 677T allele is a risk factor for leukoaraiosis, and many studies have investigated whether the MTHFR 677T allele is a risk factor for dementia, especially Alzheimer's disease. We performed a systematic review of all the 21 published articles on the relationship between the MTHFR 677T allele and dementia. Of the 21 studies, 4 used multivariate analysis. Of the remaining 17 studies, which used univariate analysis, only 4 employed matched controls. The reported adjusted OR for Alzheimer's disease was 1.54 or 1.73 for the TT genotype vs the CC genotype and 0.96 or 1.31 per T allele. None of these results are statistically significant. Although the combined unadjusted ORs for Alzheimer's disease and vascular dementia were 1.18 (95%CI; 0.94-1.49) and 1.33 (95%CI; 0.66-2.68) respectively, these estimates were undermined by the heterogeneity and the possible persence of potential confounding variables.