A haplotype of the methylenetetrahydrofolate reductase gene is protective against late-onset Alzheimer’s disease
2003; Elsevier BV; Volume: 25; Issue: 3 Linguagem: Inglês
10.1016/s0197-4580(03)00082-4
ISSN1558-1497
AutoresYosuke Wakutani, Hisanori Kowa, Masayoshi Kusumi, Kazuhiro Nakaso, Kenichi Yasui, Kenji Isoe‐Wada, Hidetaka Yano, Katsuya Urakami, Takao Takeshima, Kenji Nakashima,
Tópico(s)Trace Elements in Health
ResumoEpidemiological studies have shown that elevated plasma homocysteine (Hcy) levels play an important role in the pathogenesis of Alzheimer's disease (AD). In spite of the evidence that a C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene elevates plasma Hcy levels, the impact of the C677T polymorphism on the development of AD is controversial. Here, we performed a genetic case-control study in a Japanese population to investigate whether three polymorphisms of the MTHFR gene, C677T (Ala222Val), A1298C (Glu429Ala), and A1793G (Arg594Gln), are associated with the development of late-onset AD (LOAD). In our study, the MTHFR gene had four major regional haplotypes: Haplotype A (677C-1298A-1793G), Haplotype B (677T-1298A-1793G), Haplotype C (677C-1298C-1793G), and Haplotype D (677C-1298C-1793A). The frequency of Haplotype C in LOAD was significantly lower than that in control group. Furthermore, the benefit conferred by the presence of at least one Haplotype C was stronger in LOAD patients who lacked the ApoE ε4 allele (OR=0.293; 95% CI=0.115–0.744; P=0.010). The results indicate that Haplotype C of the MTHFR gene is protective against the development of LOAD.
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