title: The Methylenetetrahydrofolate Reductase C677T Polymorphism and Risk for Late-Onset Alzheimer's disease: Further Evidence in an Italian Multicenter Study.
abstract: A functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, namely C677T (rs1801133), results in increased Hcy levels and has been associated with risk of late-onset Alzheimer's disease (LOAD). Many investigators reported association between rs1801133 and LOAD risk in Asian populations and in carriers of the apolipoprotein E (APOE) ɛ4 allele, but recent meta-analyses suggest a contribution also in other populations, including Caucasians and/or northern Africans.
  
  
  
  To further address this issue, we performed a relatively large case-control study, including 581 LOAD patients and 468 matched controls of Italian origin. APOE data were available for a subgroup of almost 600 subjects.
  
  
  
  Genotyping for rs1801133 was performed with PCR-RFLP techniques.
  
  
  
  In the total population, the MTHFR 677T allele (OR = 1.20; 95% CI = 1.01-1.43) and carriers of the MTHFR 677T allele (CT+TT versus CC: OR = 1.34; 95% CI = 1.03-1.73) resulted in increased LOAD risk. Similarly, in APOEɛ4 carriers, we observed an increased frequency of MTHFR 677CT carriers (CT versus CC: OR = 2.82; 95% CI = 1.25-6.32). Very interestingly, also in non-APOEɛ4 carriers, both MTHFR 677T allele (OR = 1.38; 95% CI = 1.03-1.85) and MTHFR 677TT genotype (OR = 2.08; 95% CI = 1.11-3.90) were associated with LOAD. All these associations survived after corrections for age, gender, and multiple testing.
  
  
  
  The present results suggest that the MTHFR C677T polymorphism is likely a LOAD risk factor in our cohort, either in APOEɛ4 or in non-APOEɛ4 carriers.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.|Doctoral School in Genetics Oncology and Clinical Medicine, University of Siena, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stoccoro
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.
authors.forename: Pierpaola
authors.initials: P
authors.lastname: Tannorella
authors.affiliation: IRCCS, Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Salluzzo
authors.affiliation: IRCCS, Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferri
authors.affiliation: IRCCS, Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nacmias
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Neurological Clinic, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.|Interdepartmental Research Center Nutrafood Nutraceuticals and Food for Health, University of Pisa, Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.|Interdepartmental Research Center Nutrafood Nutraceuticals and Food for Health, University of Pisa, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D012723:Sex; D044465:White People / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: APOE; Alzheimer’s disease; MTHFR C677T; folate; homocysteine; methylenetetrahydrofolate reductase