The brain-derived neurotrophic factor (Val66Met) polymorphism and depression in Mexican-Americans

Department of Psychiatry & Behavioral Sciences, Center on Pharmacogenomics, University of Miami Miller School of Medicine, Miami, Florida 33136-1013, USA.
Neuroreport (Impact Factor: 1.52). 09/2007; 18(12):1291-3. DOI: 10.1097/WNR.0b013e328273bcb0
Source: PubMed


The hypothesis that brain-derived neurotrophic factor (BDNF) is involved in the pathogenesis of major depression is supported by several research findings; however, genetic studies assessing the relationship between BDNF and psychiatric disorders have produced conflicting results. We examined the effect of a BDNF polymorphism on depression susceptibility in Mexican-Americans. The single nucleotide polymorphism (Val66Met), which has been shown to have functional and behavioral effects, was genotyped in 284 depressed participants and 331 controls, showing association with depression (P=0.005). Individuals homozygous for the major allele (GG) had an increased chance of being depressed (OR=1.7 95% CI 1.17-2.47). Our findings support the association of BDNF single nucleotide polymorphism rs6265 and depression, suggesting that this polymorphism may increase susceptibility to major depression in Mexican-Americans.

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Available from: Pamela Whittaker, Jan 27, 2015
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    • "Depression and poor mental health have been long identified to be closely linked and are risk factors to alcohol abuse (Davidson, 1995; Weitzman, 2004; Briere et al., 2014). BDNF variants have also been studied for association with depressive disorders and evidence of association has been found (Ribeiro et al., 2007; Lavebratt et al., 2010; Suchanek et al., 2011; Pei et al., 2012; Rippey et al., 2013 "
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    ABSTRACT: Aims: The functional BDNF single nucleotide polymorphism (SNP) rs6265 has been associated with many disorders including schizophrenia and alcohol dependence. However, studies have been inconsistent, reporting both positive and negative associations. Comorbid alcohol dependence has a high prevalence in schizophrenia so we investigated the role of rs6265 in alcohol dependence in Australian populations of schizophrenia and alcohol-dependent patients. Methods: Two BDNF SNPs rs6265 and a nearby SNP rs7103411 were genotyped in a total of 848 individuals. These included a schizophrenia group (n = 157) and a second schizophrenia replication group (n = 235), an alcohol-dependent group (n = 231) that had no schizophrenia diagnosis and a group of healthy controls (n = 225). Results: Allelic association between rs7103411 and comorbid alcohol dependence was identified (P = 0.044) in the primary schizophrenia sample. In the replication study, we were able to detect allelic associations between both BDNF SNPs and comorbid alcohol dependence (rs6265, P = 0.006; rs7103411, P = 0.014). Moreover, we detected association between both SNPs and risk-taking behaviour after drinking (rs6265, P = 0.005; rs7103411, P = 0.009) and we detected strong association between both SNPs and alcohol dependence in males (rs6265, P = 0.009; rs7103411, P = 0.013) while females showed association with multiple behavioural measures reflecting repetitive alcohol consumption. Haplotype analysis revealed the rs6265-rs7103411 A/C haplotype is associated with comorbid alcohol dependence (P = 0.002). When these SNPs were tested in the non-schizophrenia alcohol-dependent group we were unable to detect association. Conclusion: We conclude that these BDNF SNPs play a role in development of comorbid alcohol dependence in schizophrenia while our data do not indicate that they play a role in alcohol-dependent patients who do not have schizophrenia.
    Full-text · Article · Jul 2014 · Alcohol and Alcoholism
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    • "Frielingsdorf et al. reported that Met homozygotes may have a greater risk for major depressive disorder.14 Another study found that Val homozygotes have an increased chance of depression.13 However, negative association results have also been found,15,16 and a meta-analysis involving 14 studies reported that BDNF Val66Met was not significantly associated with depression in a total sample and that a significant effect was found only in men.17 "
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    ABSTRACT: Objective We investigated possible association between depressive disorders and BDNF Val66Met and 5-HTTLPR. Brain derived neurotrophic factor (BDNF) gene and serotonin transporter (SLC6A4) gene are promising candidate genes for depressive disorders. It has been suggested that BDNF promotes the survival and differentiation of serotonergic neurons and that serotonergic transmission exerts powerful control over BDNF gene expression. Methods Final analyses were performed on 186 patients with depressive disorders and 1032 controls. Val66Met polymorphism of BDNF gene and 5-HTTLPR polymorphism of serotonin transporter gene were genotyped and allele and genotypic associations on the diagnosis of depression and age at onset of depression were analyzed. Results The 5-HTTLPR was positively associated with depressive affected status in the total sample and in females (p=0.038 for allelewise, p=0.015 for genotype-wise associations), but, not in males. The BDNF Val66Met showed no association with depression. BDNF Val66Met and 5-HTTLPR alone were not associated with age at onset of depression. Additional analysis on the interaction between BDNF Val66Met and 5-HTTLPR found a significant association with age at onset of depression in the entire patient group. This association was also found in the female but not in the male patient group. None of the positive results survived Bonferroni correction for multiple testing. Conclusion This result suggested that BDNF Val66Met and 5-HTTLPR may contribute to depressive disorders in a complex way and that the genetic effect could differ by gender. Further studies with large number of patients will be necessary.
    Full-text · Article · Apr 2014 · Psychiatry investigation
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    • "Paradoxically, Tsai SJ et al. reported a higher incidence of depression in Val, not Met carriers [20]. Currently, it is still unclear what the consequences of the Val66Met polymorphism are on the brain function, as both alleles have been associated with different disease processes, including emotion response [21], esoghageal hypersensitivity [22], individual's sexual activities [23] and depression [15,24,25]. Of interest, several studies have shown that the degree of therapeutic response to antidepressants is associated with the BDNF Val66Met polymorphism, suggesting that BDNF gene may be a good candidate gene for the pharmacogenetic study of antidepressants [7]. "
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    ABSTRACT: Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depression. Individuals with type 2 diabetes (T2DM) have a high prevalence of major depression and low levels of BDNF. We therefore explored whether the BDNF Val66Met polymorphism is associated with co-morbid depression and whether depression affects the serum levels of BDNF in a Han Chinese subjects with T2DM. A Total of 296 T2DM patients and 70 healthy volunteers (Health control, HC group) were recruited in this study. T2DM patients were divided into two subgroups: depressive diabetes group (DDM group, n = 64) and non-depressive diabetes group (NDDM group, n = 232), according to the presence or the absence of depression assessed by Center for Epidemiologic Studies Depression Scale (CES-D) and Patient Health Questionnaire-9 (PHQ-9). Val66Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Serum BDNF levels were measured by ELISA kit. In this study, 21.6 % (64/296) patients with T2DM had depression. The BDNF Val66Met genotype distributions were statistically different among the three groups (chi2 = 7.39, p < 0.05). DDM group carried the highest frequencies of Met allele (53.9 %) compared to HC group (39.3 %) and NDDM group (38.8 %). Subjects with Met/Met had lowest serum BDNF levels (76.59 +/- 5.12 pg/ml, F = 7.39, p < 0.05) compared to subjects with Val/Met (79.04 +/- 5.19 pg/ml) and Val/Val (83.83 +/- 3.97 pg/ml). Within T2DM group, it was also observed that the serum BDNF levels in DDM group were significantly lower than those in NDDM group (76.67 +/- 5.35 vs. 79.84 +/- 3.97 pg/ml, p < 0.05). In type 2 diabetes subjects, BDNF serum levels were significant correlations with genotypes (r = -0.346, p < 0.01), depression scores (r = -0.486, p < 0.01) and HbA1c (r = -0.168, p < 0.05). After adjustment for gender, HbA1c, BMI and numbers of complications, BDNF Val/Met genotype distributions (OR = 2.105, p < 0.05) and decreased serum BDNF levels (OR = 0.835, p < 0.01) were independently associated with depression in T2DM. The BDNF Val66Met polymorphism might be implicated in the pathogenesis of depression in T2DM by decreasing serum BDNF levels in Han Chinese Subjects.
    Full-text · Article · Aug 2013 · Behavioral and Brain Functions
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