Val66met polymorphism and serum brain-derived neurotrophic factor levels in bipolar disorder

Abstract

group to cytosine residues in the dinucleotide sequence CpG. 1 A lack of alimentary methyl-group donors, like folate, owing to starvation, may be the underlying cause of both elevated homocysteine and DNA hypomethylation in AN.To further investigate possible epigenetic contributions to the pathophysiology of eating disorders, we analyzed the expression and promoter-specific DNA methylation of two genes, SNCA and HERP, recently described to be altered in alcohol dependence. 5,7 We found a decreased SNCA expression in patients with AN, which was associated with a DNA hypermethylation of the SNCA promoter. Although showing a decreased expression of SNCA, we failed to find hypermethylation in the BN groups possibly owing to a lack of power of the study, as there was a trend towards hypermethylation when compared to controls (t-test; P = 0.083), but this was lost after correction for multiple comparisons. The observation that unchanged promotermethylation of the HERP gene was associated with a gene expression comparable to that in the control group may suggest that normal patterns of DNA methylation can be kept constant in the promoter regions of certain genes despite a potential lack of methyl groups.In conclusion, we found alterations of epigenetic DNA methylation in females with AN. These findings need to be replicated in a larger sample and different genes should be analyzed, and different methods of analyzing methylation patterns of the DNA should be applied. The restriction enzyme-based approach that we have chosen has some disadvantages when compared to bisulfite sequencing methods, mainly the limitation of analysis to one CpG element in the promoter and the need for reliable digestion results. Longitudinal observations, comparing acute illness with the situation after refeeding and recovery, are warranted. Profound knowledge of the epigenetics of eating disorders may help in understanding the geneenvironment nexus postulated for the disorder.

Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder

“…However, in a recent study we showed that met carriers did not present lower levels of BDNF in their sera. 7 Thus, BD patients who are met-carriers seem to be more likely to present cognitive impairment and rapid cycling; however, such findings were not correlated with lower BDNF serum levels.…”

“…12 Even though some studies have suggested an association of the val66met polymorphism and BDNF expression, negative reports on this association have been described. 7,22 In any case, genetic influences on cognition might be subtler, and involve synergic polymorphism interaction, such as the one recently demonstrated in the general population between the RE1-silencing transcription factor (REST) gene and the BDNF val66met polymorphism. 23 Our study has other limitations that must be acknowledged.…”

Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity

“…Excluded: no MDD phenotype, 8,14,67,68,[85][86][87][88][89][90][91][92][93][94][95][96][97] no case-control design, 22,31,[98][99][100][101][102][103] no adults 104,105 and no Hardy-Weinberg equilibrium (HWE). 106 Included: Caucasian studies, 11,[33][34][35][36][37][38][39][40] Asian studies 19,21,[41][42][43] and gender studies.…”

Val66Met polymorphism and serum brain‐derived neurotrophic factor in bipolar disorder: an open‐label trial

“…Genomic DNA was extracted using standard procedures (27). The genotyping of the BDNF Val66Met polymorphism was performed using a 5' nuclease TaqMan allelic discrimination assay on the Applied Biosystems 7500 Real-Time PCR Systems (Applied Biosystems, Carlsbad, CA, USA).…”