Alzheimer's disease in Brazilian elderly has a relation with homocysteine but not with MTHFR polymorphisms

Abstract

-Objective: To investigate the association between total plasma homocysteine concentration, C677T and A1298C polymorphisms in MTHFR gene and Alzheimer´s disease (AD) development. M e t h o d : F o rt y -t h ree patients with probable (63%) and possible (37%) AD and 50 non-demented controls were evaluated. Groups did not differ as to gender, age, scholar years, diabetes, alcohol and coffee intake and physical activity. Total plasma homocysteine (Hcy) levels were determined by HPLC and genotyping for MTHFR by PCR/RFLP. Mann-Whitney "U" test was used to compare quantitative variable, Fisher-F re e m a n -H a l t o n test to compare genotypes and allele pro p o rtions and Chi-square test to other qualitative variables. R e s u l t s : AD patients presented higher total plasma Hcy levels than controls and the diff e rence was statistically significant. No diff e rences in the C677T and A1298C MTHFR polymorphisms distributions were found between patients and controls. Plasma homocysteine concentration did not change with MTHFR genotypes. Conclusion: Our data confirms the association between increased plasma Hcy concentration and AD and suggests that neither C677T nor A1298C MTHFR polymorphisms contributed to genetic susceptibility for AD in elderly individuals in the Northeast of Brazil.KEY WORDS: homocysteine, MTHFR, Alzheimer's disease.A doença de Alzheimer em idosos brasileiros tem relação com homocisteina mas não com polimorfismos MTHFR RESUMO -Objetivo: Investigar a associação entre a concentração plasmática total de homocisteína (Hcy), os polimorfismos C677T e A1298C do gene MTHFR e o desenvolvimento da Doença de Alzheimer (AD). Método: Foram avaliados 43 pacientes com doença de Alzheimer possível (37%) e provável (63%) e 50 cont roles não dementes, não divergentes quanto ao sexo, idade, anos de escolaridade, diabetes, consumo de álcool e de café e vida sedentária. Os níveis plasmáticos de homocisteína foram determinados por HPLC e a genotipagem para MTHFR por PCR/RFLP. A comparação dos níveis de homocisteína foi realizada pelo teste "U" Mann-Whitney, a comparação das proporções dos genótipos e alelos pelo teste de Fisher-F re e m a nHalton e as demais variáveis qualitativas, pelo teste do qui-quadrado. Resultados: Os pacientes AD apresentaram níveis mais elevados de Hcy plamática total do que os controles e a diferença entre os grupos foi estatisticamente significante. Não houve diferença nas distribuições genotípicas C677T e A1298C entre pacientes e controles. A concentração de Hcy não variou com os genótipos. Conclusão: Nossos dados conf i rmam a associação de concentração elevada de Hcy plasmática com DA e sugerem que os polimorf i s m o s C677T e A1209C não contribuem para a susceptibilidade genética a DA em idosos do Nordeste do Brasil. PALAVRAS-CHAVE: homocisteína, MTHFR, doença de Alzheimer. M e t i l e n e t e t r a i d rofolate reductase (MTHFR) is an enzyme of the folate metabolism that reduces 5,10-m e t i l e n e t e t r a i d rofolate (5,10-mTHFR) to 5-metiltet r a i d rofolate (5-mTHF), a...

Lack of association between MTHFR A1298C variant and Alzheimer’s disease: evidence from a systematic review and cumulative meta-analysis

“…Thus, 118 publications were futher excluded. Finally, 10 eligible studies [16,19,[21][22][23][24][25][26][27][28] were recognized in this meta-analysis. The main characteristics of all these studies are listed in Table 1.…”

“…Mutations in MTHFR gene (C677T and A1298C) might cause amino acid substitutions that result in decreased enzyme activity with a reduced 5-mTHF availability. As a consequence of the MTHFR dysfunctions, Hcy level was increased in plasma [19]. High levels of plasma homocysteine can produce a cytotoxic effect [20] and compromise normal cell function in several different tissues [16] (e.g.…”

“…Several studies [16,19,[21][22][23][24][25][26][27][28] tried to find out any association between MTHFR A1298C polymorphism and the risk of AD; due to different populations, case selections, and sample sizes, the association remained inconclusive. Two articles [16,25] revealed the genetic association of MTHFR A1298C polymorphism with AD risk, but others indicated lack of this association.…”

Maternal Vitamin B Deficiency and Epigenetic Changes of Genes Involved in the Alzheimer’ s Disease Pathogenesis

“…Additionally, chronic maternal hyperhomocysteinemia may impair brain development and consequently the cognitive functions of the fetuses by the increase of neuronal vulnerability to excitotoxicity, oxidative stress and apoptosis [14,15]. High Hcy levels also constitute a risk factor for the development of cardiovascular diseases, stroke and neurodegenerative disorders, such as Alzheimer's disease (AD) [16][17][18]]. …”

Study of association between genetic polymorphisms of phospholipase A2 enzymes and Alzheimer's disease

“…Several candidate genetic polymorphisms related to systems supposedly involved with AD pathophysiology have been implicated in the susceptibility for LOAD, but none has been consistently replicated 6,7 . Brain phospholipids are interesting sites for the interaction between genes and environment because enzymes and other proteins that regulate phospholipid metabolism are clearly genetically determined 8 .…”