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Minerva Medica 2021 June;112(3):365-71

DOI: 10.23736/S0026-4806.20.06801-9

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

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

Marco ZUIN 1, 2, Carlo CERVELLATI 2 , Alessandro TRENTINI 2, Loris RONCON 2, Patrizia GUASTI 1, Giovanni ZULIANI 1

1 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy; 2 Department of Cardiology, Santa Maria delle Misericordia Hospital, Rovigo, Italy



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.
EVIDENCE ACQUISITION: 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.
EVIDENCE SYNTHESIS: 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.


KEY WORDS: Alzheimer disease; Methylenetetrahydrofolate Reductase (NADPH2); Meta-analysis; Polymorphism, genetic

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