Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to Alzheimer's disease.

No clear consensus has been reached at the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and Alzheimer's disease (AD) risk. Thus in this meta-analysis, a total of 19 case-control studies was assessed to evaluate the possible association. The data demonstrated that the frequency of T677 allele (T vs. C) was significantly associated with susceptibility to AD in all subjects (OR=1.15, 95% CI=1.06-1.26) and in East Asians (OR=1.22, 95% CI=1.08-1.39). There was statistical difference between AD patients and the controls under recessive genetic mode (CT+TT vs. CC) and homozygote comparison (TT vs. CC) in all subjects and in East Asians as well. Despite a small effect of the polymorphism on late-onset AD (LOAD) risk, MTHFR C677T polymorphism was not a major risk factor for LOAD in East Asians and Caucasians. A subgroup analysis in the subjects without APOE epsilon4 alleles showed T677 allele significantly increased risk of AD in all subjects (OR=1.21, 95% CI: 1.04-1.42) and in East Asians (OR=1.28, 95% CI: 1.06-1.55). However, no association was found in Caucasians. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing AD susceptibility in East Asians, not in Caucasians.