Association between obesity and the brain-derived neurotrophic factor gene polymorphism Val66Met in individuals with bipolar disorder in Mexican population

Mirna Edith Morales-Marín; Alma Delia Genis-Mendoza; Carlos Alfonso Tovilla-Zarate; Nuria Lanzagorta; Michael Escamilla; Humberto Nicolini

doi:10.2147/NDT.S104654

Association between obesity and the brain-derived neurotrophic factor gene polymorphism Val66Met in individuals with bipolar disorder in Mexican population

Neuropsychiatr Dis Treat. 2016 Jul 25:12:1843-8. doi: 10.2147/NDT.S104654. eCollection 2016.

Authors

Mirna Edith Morales-Marín¹, Alma Delia Genis-Mendoza², Carlos Alfonso Tovilla-Zarate³, Nuria Lanzagorta⁴, Michael Escamilla⁵, Humberto Nicolini⁶

Affiliations

¹ Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), CDMX, Mexico.
² Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), CDMX, Mexico; Psychiatric Care Services, Child Psychiatric Hospital Dr Juan N Navarro, CDMX, Mexico.
³ Genomics Research Center, Juarez Autonomous University of Tabasco, Comalcalco, Mexico.
⁴ Carracci Medical Group, CDMX, Mexico.
⁵ Department of Psychiatry, Paul L Foster School of Medicine, Texas Tech University Health Science Center, El Paso TX, USA.
⁶ Genomics of Psychiatric and Neurodegenerative Diseases Laboratory, National Institute of Genomic Medicine (INMEGEN), CDMX, Mexico; Carracci Medical Group, CDMX, Mexico.

Abstract

Background: The brain-derived neurotrophic factor (BDNF) has been considered as an important candidate gene in bipolar disorder (BD); this association has been derived from several genetic and genome-wide studies. A polymorphic variant of the BDNF (Val66Met) confers some differences in the clinical presentation of affective disorders. In this study, we evaluated a sample population from Mexico City to determine whether the BDNF (rs6265) Val66Met polymorphism is associated with the body mass index (BMI) of patients with BD.

Methods: This association study included a sample population of 357 individuals recruited in Mexico City. A total of 139 participants were diagnosed with BD and 137 were classified as psychiatrically healthy controls (all individuals were interviewed and evaluated by the Diagnostic Interview for Genetic Studies). Genomic DNA was extracted from peripheral blood leukocytes. The quantitative polymerase chain reaction (qPCR) assay was performed in 96-well plates using the TaqMan Universal Thermal Cycling Protocol. After the PCR end point was reached, fluorescence intensity was measured in a 7,500 real-time PCR system and evaluated using the SDS v2.1 software, results were analyzed with Finetti and SPSS software. Concerning BMI stratification, random groups were defined as follows: normal <25 kg/m(2), overweight (Ow) =25.1-29.9 kg/m(2), and obesity (Ob) >30 kg/m(2).

Results: In the present work, we report the association of a particular BMI phenotype with the presence of the Val66Met allele in patients with BD (P=0.0033 and odds ratio [95% confidence interval] =0.332 [157-0.703]), and correlated the risk for valine allele carriers with Ow and Ob in patients with BD.

Conclusion: We found that the methionine allele confers a lower risk of developing Ow and Ob in patients with BD. We also confirmed that the G polymorphism represents a risk of developing Ow and Ob in patients with BD. In future studies, the haplotype analysis should provide additional evidence that BDNF may be associated with BD and BMI within the Mexican population.

Keywords: bipolar disorder; body mass index; brain-derived neurotrophic factor; single nucleotide polymorphism.