Journal of Alzheimer's disease : JAD · 2017
The Methylenetetrahydrofolate Reductase C677T Polymorphism and Risk for Late-Onset Alzheimer's disease: Further Evidence in an Italian Multicenter Study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Stoccoro Andrea, Tannorella Pierpaola, Salluzzo Maria Grazia, Ferri Raffaele, Romano Corrado, Nacmias Benedetta, Siciliano Gabriele, Migliore Lucia, Coppedè Fabio
Аннотация
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) ɛ4 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 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.
CONCLUSIONS: 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.
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 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.
CONCLUSIONS: 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.