Effect of the polymorphism BDNF rs6265 G/A in Mexican outpatient children with autism spectrum disorders

Mirna Edith Morales-Marín, Miriam Aguilar, Lilia Albores, Ana Ballesteros, Xóchitl Castro, Carlos Chicalote, Amalia Gómez, Nora Gutiérrez, Nuria Lanzagorta, Fernando López, Carla Márquez, Nimsi Morales, Omar Náfate, Patricia Sánchez, Ana María Balboa, Humberto Nicolini

DOI: https://doi.org/10.17711/SM.0185-3325.2018.019


Introduction. The study of autistic spectrum disorders (ASD) at the genetic level is extremely important to understand their origin. In Mexico, there are few works addressed from this perspective.

Objective. We investigated the role of the Brain Derived Neurotrophic Factor ( BDNF ) gene variant rs6265 G/A for single nucleotide polymorphism analysis in Mexican children with ASD using a case-control association design.

Method. We made a pilot study by case-control analysis adjusting by gender, age, and ancestry.

Results. Our study found no association between the BDNF rs6265 gene polymorphism and ASD [ p = .419, OR = 1.597 (.514, 4.967)].

Discussion and conclusion. Worldwide, the results of case-control association studies with the rs6265 of BDNF are controversial and do not always replicate. This may be due to the ethnicity of our population and additional factors not studied in the present work. Our study suggests that the SNP rs6265 is not contributing for ASD susceptibility in Mexican population.


BDNF; autism spectrum disorders; single nucleotide polymorphism; Mexican population

Full Text:

HTML Pdf ePub Xml


Bourgeron, T. (2015). From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev Neurosci, 16(9), 551-563. doi:10.1038/nrn3992

Broek, J. A., Brombacher, E., Stelzhammer, V., Guest, P. C., Rahmoune, H., & Bahn, S. (2014). The need for a comprehensive molecular characterization of autism spectrum disorders. Int J Neuropsychopharmacol, 17(4), 651-673. doi:10.1017/S146114571300117X

Bryn, V., Halvorsen, B., Ueland, T., Isaksen, J., Kolkova, K., Ravn, K., & Skjeldal, O. H. (2015). Brain derived neurotrophic factor (BDNF) and autism spectrum disorders (ASD) in childhood. Eur J Paediatr Neurol, 19(4), 411-414. doi:10.1016/j.ejpn.2015.03.005

Cheng, L., Ge, Q., Xiao, P., Sun, B., Ke, X., Bai, Y., & Lu, Z. (2009). Association study between BDNF gene polymorphisms and autism by three-dimensional gel-based microarray. Int J Mol Sci, 10(6), 2487-2500. doi:10.3390/ijms10062487

Diaz-Anzaldua, A., & Diaz-Martinez, A. (2013). [Genetic, environmental, and epigenetic contribution to the susceptibility to autism spectrum disorders]. Rev Neurol, 57(12), 556-568.

Fombonne, E., Marcin, C., Manero, A. C., Bruno, R., Diaz, C., Villalobos, M., . . . Nealy, B. (2016). Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey. J Autism Dev Disord, 46(5), 1669-1685. doi:10.1007/s10803-016-2696-6

Halepoto, D. M., Bashir, S., & L, A. L. A. (2014). Possible role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder: current status. J Coll Physicians Surg Pak, 24(4), 274-278. doi:04.2014/JCPSP.274278

Ingram, J. L., Stodgell, C. J., Hyman, S. L., Figlewicz, D. A., Weitkamp, L. R., & Rodier, P. M. (2000). Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology, 62(6), 393-405. doi:10.1002/1096-9926(200012)62:6<393::AID-TERA6>3.0.CO;2-V

Kasarpalkar, N. J., Kothari, S. T., & Dave, U. P. (2014). Brain-Derived Neurotrophic Factor in children with Autism Spectrum Disorder. Ann Neurosci, 21(4), 129-133. doi:10.5214/ans.0972.7531.210403

Kim, B. N., Cummins, T. D., Kim, J. W., Bellgrove, M. A., Hong, S. B., Song, S. H., . . . Han, D. H. (2011). Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val(6)(6)Met polymorphism is associated with a better response to OROS-MPH in Korean ADHD children. Int J Neuropsychopharmacol, 14(10), 1399-1410. doi:10.1017/S146114571100099X

Lai, M. C., Lombardo, M. V., Chakrabarti, B., & Baron-Cohen, S. (2013). Subgrouping the autism "spectrum": reflections on DSM-5. PLoS Biol, 11(4), e1001544. doi:10.1371/journal.pbio.1001544

Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord, 24(5), 659-685.

Marquez, L., Camarena, B., Hernandez, S., Loyzaga, C., Vargas, L., & Nicolini, H. (2013). Association study between BDNF gene variants and Mexican patients with obsessive-compulsive disorder. Eur Neuropsychopharmacol, 23(11), 1600-1605. doi:10.1016/j.euroneuro.2013.08.001

Márquez-Caraveo, Guía clínica: Trastornos Generalizados del Desarrollo. Guías del Hospital Psiquiátrico Infantil “Dr. Juan N. Navarro”. Secretaria de Salud, México. 2009.

Meng, W. D., Sun, S. J., Yang, J., Chu, R. X., Tu, W., & Liu, Q. (2016). Elevated Serum Brain-Derived Neurotrophic Factor (BDNF) but not BDNF Gene Val66Met Polymorphism Is Associated with Autism Spectrum Disorders. Mol Neurobiol. doi:10.1007/s12035-016-9721-9

Morales-Marin, M. E., Genis-Mendoza, A. D., Tovilla-Zarate, C. A., Lanzagorta, N., Escamilla, M., & Nicolini, H. (2016). Association between obesity and the brain-derived neurotrophic factor gene polymorphism Val66Met in individuals with bipolar disorder in Mexican population. Neuropsychiatr Dis Treat, 12, 1843-1848. doi:10.2147/NDT.S104654

Nishimura, K., Nakamura, K., Anitha, A., Yamada, K., Tsujii, M., Iwayama, Y., . . . Mori, N. (2007). Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism. Biochem Biophys Res Commun, 356(1), 200-206. doi:10.1016/j.bbrc.2007.02.135

Pruunsild, P., Kazantseva, A., Aid, T., Palm, K., & Timmusk, T. (2007). Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics, 90(3), 397-406. doi:10.1016/j.ygeno.2007.05.004

Raznahan, A., Toro, R., Proitsi, P., Powell, J., Paus, T., P, F. B., & Murphy, D. G. (2009). A functional polymorphism of the brain derived neurotrophic factor gene and cortical anatomy in autism spectrum disorder. J Neurodev Disord, 1(3), 215-223. doi:10.1007/s11689-009-9012-0

Ricci, S., Businaro, R., Ippoliti, F., Lo Vasco, V. R., Massoni, F., Onofri, E., . . . Archer, T. (2013). Altered cytokine and BDNF levels in autism spectrum disorder. Neurotox Res, 24(4), 491-501. doi:10.1007/s12640-013-9393-4

Sheikh, H. I., Hayden, E. P., Kryski, K. R., Smith, H. J., & Singh, S. M. (2010). Genotyping the BDNF rs6265 (val66met) polymorphism by one-step amplified refractory mutation system PCR. Psychiatr Genet, 20(3), 109-112. doi:10.1097/YPG.0b013e32833a2038

Yang, X., Liu, P., Sun, J., Wang, G., Zeng, F., Yuan, K., . . . Tian, J. (2012). Impact of brain-derived neurotrophic factor Val66Met polymorphism on cortical thickness and voxel-based morphometry in healthy Chinese young adults. PLoS One, 7(6), e37777. doi:10.1371/journal.pone.0037777

Yoo, H. J., Yang, S. Y., Cho, I. H., Park, M., & Kim, S. A. (2014). Polymorphisms of BDNF gene and autism spectrum disorders: family based association study with korean trios. Psychiatry Investig, 11(3), 319-324. doi:10.4306/pi.2014.11.3.319

Zhai, J., Yu, Q., Chen, M., Gao, Y., Zhang, Q., Li, J., . . . Qiao, J. (2013). Association of the brain-derived neurotrophic factor gene G196A rs6265 polymorphisms and the cognitive function and clinical symptoms of schizophrenia. Int J Clin Exp Pathol, 6(8), 1617-1623.