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Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/215

Título: Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/TrkB signaling in autism
Autor: Correia, C.T.
Coutinho, A.M.
Sequeira, A.F.
Sousa, I.G.
Lourenço Venda, L.
Almeida, J.P.
Abreu, R.L.
Lobo, C.
Miguel, T.S.
Conroy, J.
Cochrane, L.
Gallagher, L.
Gill, M.
Ennis, S.
Oliveira, G.G.
Vicente, A.M.
Palavras-chave: Autism
BDNF
Genetic association
Heritability
NTRK2
Perturbações do Desenvolvimento Infantil e Saúde Mental
Issue Date: Oct-2010
Editora: Genes, Brain and Behavior
Citação: Genes Brain Behav. 2010 Oct;9(7):841-8. Epub 2010 Aug 19
Resumo: The brain-derived neurotrophic factor (BDNF), a neurotrophin fundamental for brain development and function, has previously been implicated in autism. In this study, the levels of BDNF in platelet-rich plasma were compared between autistic and control children, and the role of two genetic factors that might regulate this neurotrophin and contribute to autism etiology, BDNF and NTRK2, was examined. We found that BDNF levels in autistic children (n = 146) were significantly higher (t = 6.82; P < 0.0001) than in control children (n = 50) and were positively correlated with platelet serotonin distribution (r = 0.22; P = 0.004). Heritability of BDNF was estimated at 30% and therefore candidate genes BDNF and NTRK2 were tested for association with BDNF level distribution in this sample, and with autism in 469 trio families. Genetic association analysis provided no evidence for BDNF or NTRK2 as major determinants of the abnormally increased BDNF levels in autistic children. A significant association with autism was uncovered for six single nucleotide polymorphisms (SNPs) [0.004 (Z((1df)) = 2.85) < P < 0.039 (Z((1df)) = 2.06)] and multiple haplotypes [5 × 10(-4) (χ((3df)) = 17.77) < P < 0.042 (χ((9df)) = 17.450)] in the NTRK2 gene. These results do not withstand correction for multiple comparisons, however, reflect a trend toward association that supports a role of NTRK2 as a susceptibility factor for the disorder. Genetic variation in the BDNF gene had no impact on autism risk. By substantiating the previously observed increase in BDNF levels in autistic children in a larger patient set, and suggesting a genetic association between NTRK2 and autism, this study integrates evidence from multiple levels supporting the hypothesis that alterations in BDNF/tyrosine kinase B (TrkB) signaling contribute to an increased vulnerability to autism.
Arbitragem científica: yes
URI: http://hdl.handle.net/10400.18/215
ISSN: 1601-1848
doi: 10.1111/j.1601-183X.2010.00627.x
Versão do Editor: http://onlinelibrary.wiley.com/doi/10.1111/j.1601-183X.2010.00627.x/abstract;jsessionid=AAE6FBCD672CD68780382A3A6FC7A91C.d02t02
Appears in Collections:DPSPDNT - Artigos em revistas internacionais

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