Methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism and susceptibility to late-onset Alzheimer's disease in the Italian population. A systematic review and meta-analysis.

BACKGROUND This study is a meta-analysis of the published studies on the relationship between methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism and the risk of lateonset Alzheimer's disease (LOAD) in Italian cohorts. METHODS We conducted a search on the electronic databases PubMed/Medline, Web of Science and Scopus. All cohort and case-control studies investigating the association between MTHFR 677T polymorphism and LOAD in Italian population published any time to May 8, 2020 were included in the analysis. RESULTS From an initial screening of 136 articles, 4 were included into the systemic review. The pooled analysis based on the co-dominant model revealed that the MTHFR C677T polymorphism was associated with a significant risk of LOAD among Italian cohorts (TC vs. CC: OR=1.20, 95% CI=1.06-1.36, p=0.004, I2=0%). Conversely, the pooled analysis based on the allelic model demonstrated a non-significant relationship between the MTHFR C677T polymorphism and susceptibility to LOAD in Italians (OR: 1.25, 95% CI: 0.99-1.59, p=0.060, I2=14.6%). Moreover, Italian subjects with MTHFR 677TT genotype resulted to have a significantly increased susceptibility to LOAD (OR: 1.75, 95% CI:1.23-2.50, p=0.002, I2=0%). CONCLUSIONS The present meta-analysis showed only trend of association between MTHFR C677T polymorphism and LOAD in Italian population; however, it also demonstrated an increased susceptibility of LOAD in patients having MTHFR 677TT genotype. Further studies are needed to establish whether MTHFR polymorphisms can be used as non-invasive biomarker for LOAD.