期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 56, 期 4, 页码 1451-1457出版社
IOS PRESS
DOI: 10.3233/JAD-161081
关键词
Alzheimer's disease; APOE; folate; homocysteine; methylenetetrahydrofolate reductase; MTHFR C677T
资金
- Italian Ministry of Health
Background: 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) epsilon 4 allele, but recent meta-analyses suggest a contribution also in other populations, including Caucasians and/or northern Africans. Objective: 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. Methods: Genotyping for rs1801133 was performed with PCR-RFLP techniques. Results: 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 APOE epsilon 4 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-APOE epsilon 4 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. Conclusions: The present results suggest that the MTHFR C677T polymorphism is likely a LOAD risk factor in our cohort, either in APOE epsilon 4 or in non-APOE epsilon 4 carriers.
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