Apolipoprotein E, Methylenetetrahydrofolate Reductase(MTHFR) Mutation and the Risk of Senile Dementia. An Epidemiological Study Using the Polymerase Chain Reaction(PCR) Method.

Nishiyama, Midori; Kato, Yukie; Hashimoto, Michiyo; Yukawa, Satoru; Omori, Kazuhiko

doi:10.2188/jea.10.163

Cited by 52 publications

(37 citation statements)

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“…17,25 Although we did not analyze cognitive function in the present study, an association between impaired cognitive function and SBI and white matter lesions has also been reported. 14,22 In several studies, the MTHFR TT genotype has also been demonstrated to be a risk factor for dementia, 26,27 although conflicting results have also been reported. 28,29 These findings suggest a possible association between the MTHFR TT genotype and cognitive impairment in the general population.…”

Section: Kohara Et Al Mthfr Gene and Silent Brain Infarctsmentioning

confidence: 99%

MTHFR Gene Polymorphism as a Risk Factor for Silent Brain Infarcts and White Matter Lesions in the Japanese General Population

Kohara

Fujisawa

Ando

et al. 2003

Stroke

103

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Background and Purpose-Silent brain infarcts (SBI) and white matter lesions are relatively common neuroimaging findings, especially in the elderly population. The genetic background for SBI and white matter lesions in a large Japanese general population was investigated. Methods-Subjects were recruited from participants in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation and brain MRI examination were performed in 1721 subjects free of any history of stroke. SBI and white matter lesions were diagnosed from MRI findings. Results-Of 1721 MRI examinations, SBI was observed in 178 (10.3%). The prevalence of SBI and white matter lesions increased with age. Key Words: amine oxidoreductases Ⅲ brain infarction Ⅲ elderly Ⅲ polymorphism Ⅲ white matter S ilent brain infarcts (SBI) and white matter lesions, which are often incidentally identified during CT or MRI scanning in asymptomatic individuals, are relatively common neuroimaging findings, especially in the elderly population. 1-3 However, the presence of SBI and white matter lesions has been identified as an independent risk factor for the development of future symptomatic stroke 4,5 and dementia. 6 Accordingly, the underlying mechanisms have been the focus of much research. [1][2][3]7,8 Population-based studies have been performed to identify risk factors for SBI. 2,3 It has been demonstrated that classic risk factors such as hypertension and smoking are involved in the development of SBI. [1][2][3]7,8 The genetic predisposition to SBI has also been studied. 9,10 However, a population-based study to identify a candidate gene for SBI has not been performed.Methylenetetrahydrofolate reductase (MTHFR) catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl donor in the reaction converting homocysteine (Hcy) to methionine. 11,12 An increased plasma Hcy level has consistently been shown to be an independent risk factor for atherosclerotic disorders in several meta-analyses. 11-13 On the other hand, a common mutation of MTHFR, which results in a mild increase in the plasma level of Hcy, has not been reported as a consistent risk factor for atherothrombotic disorders, including stroke. 11,12,14 Although there could be several possible mechanisms underlying the discrepancy, the sampling of cases and controls might account for part of the discrepancy.Two studies have evaluated the association between MTHFR gene C677T mutations and SBI. 9,10 Both studies failed to demonstrate significant associations. One evaluated subjects undergoing medical checkup. 9 To evaluate the genetic predisposition to SBI, community-based sampling of subjects would be less biased in the selection of cases and controls and would eliminate regional differences. Another study evaluated community-dwelling elderly subjects 10 ; however, the number of subjects was too small to reach a conclusion. The National Institute for Longevity ...

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Section: Kohara Et Al Mthfr Gene and Silent Brain Infarctsmentioning

confidence: 99%

MTHFR Gene Polymorphism as a Risk Factor for Silent Brain Infarcts and White Matter Lesions in the Japanese General Population

Kohara

Fujisawa

Ando

et al. 2003

Stroke

103

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“…Blood samples were stored at 20 o C for analysis. APOE genotyping was performed by amplification of the third exon of the APOE gene by polymerase chain reaction (PCR) with primers described by Wenham et al 23 , followed by an enzymatic clivage with the restriction enzyme HhaI (RFLP) 20 . Fragments of 72bp and 48bp are produced in APOE4, fragments of 91bp and 83bp are produced in APOE2 an 91bp and 48bp are generated in APOE3.…”

Section: Methodsmentioning

confidence: 99%

“…It has been recently reported a C677T mutation on the MTHFR gene which produces a thermolabile variant. In its homozygous form, this variant possesses a reduced overall enzyme activity to less than 30% of normal, resulting on increased serum homocysteine levels 9,20 . We examined both the APOE polymorphism and MTHFR mutation in a group of AD individuals and in controls, to assess whether these genetic factors increase the risk for this illness.…”

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confidence: 99%

Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE?

Fernandez

Scheibe

2005

Arq. Neuro-Psiquiatr.

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-Background: The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as risk factors for the occurence of Alzheimer's disease (AD) is still controversial: Objective: To verify the association between MTHFR and apolipoprotein E (APOE) polymorphisms and Alzheimer's disease. Method: This work was conducted as a case-control study. Cases included thirty patients with probable AD. Controls were constituted by 29 individuals without dementia according to neuropsychological tests paired to age, sex, race and educational level. DNA was isolated from peripheral leukocytes of anticoagulated venous blood. Genotyping of APOE and MTHFR were performed by DNA amplification and digestion. The frequences of APOE and MTHFR genotypes were submitted by chi-square test corrected by Fisher test; the APOE genotypes, to chi-square linear tendency test and the frequences of MTHFR mutant and AD, by stratificated anlysis adjust by Mantel-Haenszel method. Results: There was significant difference about APOE4 and APOE2 in the groups. (p=0.002) The odds ratio increased exponentially with the increased number of E4 allele (χ 2 linear tendency test). No significant difference was detected on MTHFR genotypes in both case and control groups. Conclusion: The APOE4 is a risk factor and demonstrated a dose-depenent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.KEY WORDS: Alzheimer's disease, apolipoprotein E, methylenetetrahydrofolate reductase, PCR-RFLP, risk factors. Polimorfismo da MTHFR é um fator de risco para demência de Alzheimer como APOE?RESUMO -Introdução: O papel do polimorfismo do gene da metilenotetrahidrofolato redutase (MTHFR) como um fator de risco para demência de Alzheimer (DA) é controverso ainda. Objetivo: Verificar a associação entre os polimorfismos da MTHFR e apolipoproteína E (APOE) e DA. Método: O trabalho foi conduzido como um estudo caso-controle. Trinta pacientes com DA provável foram incluídos no grupo caso. Vinte e nove indivíduos sem demência comprovadas por testes neuropsicológicos, emparelhados pela idade, sexo, cor e nível educacional constituíram o grupo controle. DNA foi isolado de leucócitos periféricos extraídos de sangue venoso anticoagulado. Genótipos de APOE e MTHFR foram realizados por amplificação de DNA e digestão. As freqüências dos genótipos da APOE e MTHFR foram submetidas ao teste do chi-quadrado corrigido pelo teste de Fisher; os genótipos da APOE, ao teste do chi-quadrado com tendência linear e as freqüên-cias da MTHFR mutante e DA à análise estratificada corrigida pelo método de Mantel-Haenszel. Resultados: Houve diferença significativa entre APOE4 e APOE2 nos grupos (p=0,002). O odds ratio aumentou exponencialmente com o aumento do número de alelo E4 (teste χ 2 com tendência linear). Nenhuma diferença significativa foi detectada nos genótipos da MTHFR em ambos grupos caso e controle. Conclusão: O alelo APOE4 é um fator de risco e demonstrou efeito dose-dependente enquanto o alelo E2 conferiu proteção para DA. A mut...

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“…MTHFR polymorphism causes decreased enzymatic activity of MTHFR and increased of the plasma total homocysteine level. Mutation in MTHFR is slightly associated with the onset of senile dementia (Nishiyama et al, 2000). Genotypes and haplotypes of the MTHFR have important implication for the pathogenesis of AD (Bi et al, 2009;Dorszewska et al, 2007;Gorgone et al, 2009;Kim et al, 2008;Wakutani et al, 2004).…”

Section: Methylenetetrahydrofolate Reductasementioning

confidence: 99%