Methylenetetrahydrofolate reductase C667T polymorphism and susceptibility to late-onset Alzheimer's disease in the Italian population

INTRODUCTION: This study is a meta-analysis of the published studies on the relationship between methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism and the risk of late- onset Alzheimer's disease (LOAD) in Italian cohorts. EVIDENCEACQUISITION: 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 MTHFR677T polymorphism and LOADin Italian population published any time to May 8, 2020 were included in the analysis. EVIDENCESYNTHESIS: 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 LOADin 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 LOADin Italian population; however, it also demonstrated an increased susceptibility of LOADin patients having MTHFR 677TT genotype. Further studies are needed to establish whether MTHFRpolymorphisms can be used as non-invasive biomarker for LOAD.