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The synergistic risk effect of apolipoprotein ε4 and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) haplotype for Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is a complex and multifactorial disease with the contribution of several genes and polymorphisms to its development. Among these genes, the APOEε4 is the best known risk factor for AD. Methylation is associated with APOE expression and AD development. Recently, we found an association of the TGG haplotype in the DNMT3B gene, one of the catalyst enzyme for methylation, with AD. Therefore, the objective of the study was to investigate whether APOEε4 and TGG haplotype have an synergistic effect on AD. The sample was composed of 212 Caucasian individuals (108 healthy controls and 104 with AD by NINCDS-ADRDA and DSM-IV-TR criteria) from southern Brazil. The genetic analyses were performed by real time PCR for TaqMan® assay. Multivariate logistic regression was performed categorizing groups according to presence of APOEε4 and/or TGG haplotype as an independent variable for outcome AD. The presence of TGG haplotype plus the allele APOEε4 were strongly associated with AD [OR 11.13; 95 % CI (4.25–29.16); P < 0.001]. This association had a higher risk than each risk factor alone. We found a strong association of the interaction of DNMT3B gene with the APOEε4 in this sample of AD patients. The presence of TGG haplotype and APOEε4 significantly increased the risk of developing the disease, showing an synergistic effect.

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Acknowledgments

We are grateful for the support given to this research by National Council for Scientific and Technological Development (CNPq).

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Authors and Affiliations

  1. Post Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua: Taquara 564/306 Bairro Petrópolis, Porto Alegre, RS, 90460210, Brazil

    Cíntia Monique Boschmann Ens de Bem, Julio Carlos Pezzi, Marilu Fiegenbaum & Analuiza Camozzato

  2. Neurology Service, Dementia Clinic, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Ericksen Mielle Borba & Marcia Lorena Fagundes Chaves

  3. UniRitter Laureate International Universities, Porto Alegre, RS, Brazil

    Fabiana Michelsen de Andrade

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  1. Cíntia Monique Boschmann Ens de Bem
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  2. Julio Carlos Pezzi
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Correspondence to Analuiza Camozzato.

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de Bem, C.M.B.E., Pezzi, J.C., Borba, E.M. et al. The synergistic risk effect of apolipoprotein ε4 and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) haplotype for Alzheimer’s disease. Mol Biol Rep 43, 653–658 (2016). https://doi.org/10.1007/s11033-016-3999-6

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  • DOI: https://doi.org/10.1007/s11033-016-3999-6

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