title: A haplotype of the methylenetetrahydrofolate reductase gene is protective against late-onset Alzheimer's disease.
abstract: Epidemiological 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 4 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.
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago 683-8504, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Wakutani
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kowa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kusumi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaso
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yasui
authors.forename: Kenji
authors.initials: K
authors.lastname: Isoe-Wada
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yano
authors.forename: Katsuya
authors.initials: K
authors.lastname: Urakami
authors.forename: Takao
authors.initials: T
authors.lastname: Takeshima
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000097:blood; D001921:Brain / Q000201:enzymology*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics*; D006710:Homocysteine / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)