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The GAB2 and BDNF polymorphisms and the risk for late-onset Alzheimer's disease in an elderly Brazilian sample

Published online by Cambridge University Press:  08 April 2015

Renalice Neves Vieira ,
Joalce Dornelas Magalhães ,
Jemima Sant’Anna ,
Mateus Massao Moriguti ,
Débora Marques de Miranda ,
Luiz De Marco ,
Edgar Nunes de Moraes ,
Marco Aurélio Romano-Silva ,
Maria Aparecida Camargos Bicalho  and
Jonas Jardim de Paula
...Show all authors
Renalice Neves Vieira*
Affiliation:
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100Brazil
Joalce Dornelas Magalhães
Affiliation:
Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Jemima Sant’Anna
Affiliation:
Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Mateus Massao Moriguti
Affiliation:
Academy Medical, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Débora Marques de Miranda
Affiliation:
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100Brazil Department of Pediatrics, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Luiz De Marco
Affiliation:
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100Brazil Department of Surgery, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Edgar Nunes de Moraes
Affiliation:
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100Brazil Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Marco Aurélio Romano-Silva
Affiliation:
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100Brazil Department of Mental Health, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Maria Aparecida Camargos Bicalho
Affiliation:
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100Brazil Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
Jonas Jardim de Paula
Affiliation:
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100Brazil
Marco Túlio Gualberto Cintra
Affiliation:
Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Brazil
*
Correspondence should be addressed to: Renalice Neves Vieira, INCT de Medicina Molecular, Av. Professor Alfredo Balena, 190, Santa Efigênia, 30.130-100, Belo Horizonte, Minas Gerais, Brasil. Phone: +55 31 8854-5208. Email: renalicevieira@gmail.com.
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Abstract

Background:

Evidences suggest that GAB2 and BDNF genes may be associated with Alzheimer's disease (AD). We aimed to investigate the GAB2 rs2373115 and BDNF rs6265 polymorphisms and the risk of AD in a Brazilian sample.

Methods:

269 AD patients and 114 controls were genotyped with Real-time PCR. Multifactor dimensionality reduction (MDR) was employed to explore the effects of gene–gene interactions.

Results:

GAB2 and BDNF were not associated with AD in our sample. Nevertheless BDNF Val allele (rs6265) presented a synergic association with the APOE ε4 allele. A multiple logistic regression demonstrated that the APOE ε4 allele and years of education were the best predictors for AD. In ε4 non-carriers sex, education and hypertension were independently correlated with AD, while in ε4 carriers we did not observe any association. The findings were further confirmed by bootstrapping method.

Conclusions:

Our data suggest that the interaction of BDNF and APOE has significant effect on AD. Moreover in absence of ε4, female sex, low level of education and hypertension are independently associated with AD. Interventions aimed to prevent AD should focus on these factors and also taking into account the APOE alleles.

Keywords

Alzheimer’s diseaseGAB2BDNFAPOErisk factors
Type
Research Article
Information
International Psychogeriatrics , Volume 27 , Special Issue 10: Psychosocial and Ethical Aspects of Dementia , October 2015 , pp. 1687 - 1692
Copyright
Copyright © International Psychogeriatric Association 2015 

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References

Adamczuk, K.et al. (2013). Clinical Polymorphism of brain derived neurotrophic factor influences β amyloid load in cognitively intact apolipoprotein E ε4 carriers. NeuroImage, 2, 512–520. doi:10.1016/j.nicl.2013.04.001.CrossRefGoogle Scholar
Bastos-Rodrigues, L., Pimenta, J. R. and Pena, S. D. J. (2006). The genetic structure of human populations studied through short insertion-deletion polymorphisms. Annals of Human Genetics, 70, 658–665. doi: 10.1111/j.1469-1809.2006.00287.x.CrossRefGoogle ScholarPubMed
Bicalho, M. A. C.et al. (2013). Sociodemographic characteristics, clinical factors, and genetic polymorphisms associated with Alzheimer's disease. International Journal of Geriatric Psychiatry, 28, 640–646. doi:10.1002/gps.3875.CrossRefGoogle ScholarPubMed
Brunelli, A. (2014). A synopsis of resampling techniques. Journal of Thoracic Disease, 6, 1879–1882. doi:10.3978/j.issn.2072-1439.2014.09.09.Google ScholarPubMed
Diniz, B. S. and Teixeira, A. L. (2011). Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and beyond. Neuromolecular Medicine, 13, 217–222. doi: 10.1007/s12017-011-8154-x.CrossRefGoogle ScholarPubMed
Duron, E. and Hanon, O. (2008). Vascular risk factors, cognitive decline, and dementia. Vascular Health and Risk Management, 4, 363–381. doi: 10.2147/VHRM.S1839.Google ScholarPubMed
Eichner, J. E.et al. (2002). Apolipoprotein E Polymorphism and cardiovascular disease: a HuGE review. American Journal of Epidemiology, 155, 487–495. doi: 10.1093/aje/155.6.487.CrossRefGoogle ScholarPubMed
Garibotto, V.et al. (2012). Education and occupation provide reserve in both ApoE ε4 carrier and noncarrier patients with probable Alzheimer's disease. Neurological Sciences, 33, 1037–1042. doi:10.1007/s10072-011-0889-5.CrossRefGoogle ScholarPubMed
Jin, C.et al. (2013). GAB2 polymorphism rs2373115 confers susceptibility to sporadic Alzheimer's disease. Neuroscience Letters, 556, 216–220. doi:10.1016/j.neulet.2013.10.036.CrossRefGoogle ScholarPubMed
Kauppi, K., Nilsson, L. G., Persson, J. and Nyberg, L. (2014). Additive genetic effect of APOE and BDNF on hippocampus activity. NeuroImage, 89, 306–313. doi:10.1016/j.neuroimage.2013.11.049.CrossRefGoogle ScholarPubMed
Kim, J., Basak, J. M. and Holtzman, D. M. (2009). Role of apolipoprotein E in Alzheimer's disease. Neuron, 63, 287–303. doi:10.1016/j.neuron.2009.06.026.CrossRefGoogle ScholarPubMed
Lahiri, D. K. and Nurnberger, J. I. Jr. (1991). A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Research, 19, 5444. doi: 10.1093/nar/19.19.5444.CrossRefGoogle ScholarPubMed
Leduc, V., Jasmin-Bélanger, S. and Poirier, J. (2010). APOE and cholesterol homeostasis in Alzheimer's disease. Trends in Molecular Medicine, 16, 469–477. doi: 10.1016/j.molmed.2010.07.008.CrossRefGoogle ScholarPubMed
Liu, Y.H.et al. (2014). Associations between ApoE ε4 carrier status and serum BDNF levels-new insights into the molecular mechanism of ApoE ε4 actions in Alzheimer's disease. Molecular Neurobiology. Epublished ahead of print, doi:10.1007/s12035-014-8804-8.CrossRefGoogle Scholar
Medway, C. and Morgan, K. (2014). Review: the genetics of Alzheimer's disease; putting flesh on the bones. Neuropathology and Applied Neurobiology, 40, 97–105. doi:10.1111/nan.12101.CrossRefGoogle ScholarPubMed
Mesulam, M. M. (1999). Neuroplasticity failure in Alzheimer's disease: bridging the gap between plaques and tangles. Neuron, 24, 521–529. doi: 10.1016/S0896-6273(00)81109-5.CrossRefGoogle Scholar
Mielke, M. M., Vemuri, P. and Rocca, W. A. (2014). Clinical epidemiology of Alzheimer's disease: assessing sex and gender differences. Clinical Epidemiology, 6, 37–48. doi: 10.2147/CLEP.S37929.CrossRefGoogle ScholarPubMed
Moore, J. H. (2004). Computational analysis of gene-gene interaction using multifactor dimensionality reduction. Expert Review of Molecular Diagnostics, 4, 795–803. doi:10.1586/14737159.4.6.795.CrossRefGoogle ScholarPubMed
Pritchard, J. K., Stephens, M. and Donnelly, P. (2000). Inference of population structure using multilocus genotype data. Genetics, 155, 945–959.CrossRefGoogle ScholarPubMed
R Core Team (2013). R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Available at: http://www.R-project.org/. Accessed 14 may 2014.Google Scholar
Reiman, E. M.et al. (2007). GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers. Neuron 54, 713–720. doi:10.1016/j.neuron.2007.05.022.CrossRefGoogle ScholarPubMed
Reitz, C. and Mayeux, R. (2014). Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochemical Pharmacology, 88, 640–651. doi:10.1016/j.bcp.2013.12.024.CrossRefGoogle ScholarPubMed
Roe, C. M.et al. (2007). Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis. Neurology, 68, 223–228. doi:10.1212/01.wnl.0000251303.50459.8a.CrossRefGoogle ScholarPubMed
Sapkota, S., Vergote, D., Westaway, D., Jhamandas, J. and Dixon, R. A. (2015). Synergistic associations of catechol-O-methyltransferase and brain-derived neurotrophic factor with executive function in aging are selective and modified by apolipoprotein E. Neurobiology of Aging, 36, 249–256. doi:10.1016/j.neurobiolaging.2014.06.020.CrossRefGoogle ScholarPubMed
Scazufca, M.et al. (2008). Risk factor across the life course and dementia in a Brazilian population: results from the Sao Paulo Ageing & Health Study (SPAH). International Journal of Epidemiology, 37, 879–890. doi: 10.1093/ije/dyn125.CrossRefGoogle Scholar
Soldan, A.et al. (2013). Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease. Neurobiology of Aging, 34, 2827–2834. doi:10.1016/j.neurobiolaging.2013.06.017.CrossRefGoogle Scholar
Steyerberg, E. W., Harrell, F. E., Borsboom, G. J. J. M., Eijkemans, M. J. C., Vergouwe, Y. and Habbema, J. D. F. (2001). Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. Journal of Clinical Epidemiology, 54, 774–781. doi: 10.1016/S0895-4356(01)00341-9.CrossRefGoogle ScholarPubMed
Tanzi, R. E. (2012). The genetics of Alzheimer disease. Cold Spring Harbor Perspectives in Medicine, 2, a006296. doi: 10.1101/cshperspect.a006296.CrossRefGoogle ScholarPubMed
Verghese, P. B., Castellano, J. M. and Holtzman, D. M. (2011). Roles of apolipoprotein E in Alzheimer's disease and other neurological disorders. Lancet Neurology, 10, 241–252. doi: 10.1016/S1474-4422(10)70325-2.CrossRefGoogle ScholarPubMed
Ward, D. D., Summers, M. J., Saunders, N. L., Janssen, P., Stuart, K. E. and Vickers, J. C. (2014). APOE and BDNF Val66Met polymorphisms combine to influence episodic memory function in older adults. Behavioural Brain Research, 271, 309—315. doi:10.1016/j.bbr.2014.06.022.CrossRefGoogle ScholarPubMed
Zou, F.et al. (2013). Linking protective GAB2 variants, increased cortical GAB2 expression and decreased Alzheimer's disease pathology. PloS one, 8, e64802. doi:10.1371/journal.pone.0064802.CrossRefGoogle ScholarPubMed