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

• Published in: Molecular psychiatry Vol. 15; no. 3; pp. 260 - 271
• Main Authors: Verhagen, M, van der Meij, A, van Deurzen, P A M, Janzing, J G E, Arias-Vásquez, A, Buitelaar, J K, Franke, B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2010; Nature Publishing Group
• Subjects: Alleles; Antidepressants; Asian Continental Ancestry Group - genetics; Behavioral Sciences; Biological Psychology; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Demographic aspects; Depressive Disorder, Major - genetics; Ethnicity; Etiology; European Continental Ancestry Group - genetics; Female; Gender; Gene frequency; Gene polymorphism; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Health aspects; Humans; Major depressive disorder; Male; Medicine; Medicine & Public Health; Mental depression; Meta-analysis; Middle Aged; Minority & ethnic groups; Nerve growth factor; Neural coding; Neurosciences; original-article; Pharmacotherapy; Phenotypes; Polymorphism; Polymorphism, Single Nucleotide; Psychiatry; Risk factors; Sex Characteristics; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Systematic review; Netherlands; meta-analysis; Val66Met; major depressive disorder; gender; ethnicity
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2008.109

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes. However, genetic association studies of the BDNF Val66Met polymorphism (single nucleotide polymorphism rs6265) in major depressive disorder (MDD) have produced inconsistent results. We conducted a meta-analysis of studies comparing the frequency of the BDNF Val66Met-coding variant in depressed cases (MDD) and nondepressed controls. A total of 14 studies involving 2812 cases with DSM-III or -IV defined MDD and 10 843 nondepressed controls met the inclusion criteria. Analyses were stratified either by gender or ethnicity (Asian and Caucasian) because MDD is more prevalent in women and in Caucasians and because BDNF allele frequencies differ by ethnicity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were provided for allelic analyses (Met versus Val), as well as for genotypic analyses (Met/Met and Val/Met versus Val/Val). In the total sample, the BDNF Val66Met polymorphism was not significantly associated with depression. However, the gender stratified analyses revealed significant effects in both the allelic and genotypic analyses in men (OR MET , 95% CI; 1.27 (1.10–1.47); OR MET/MET , 95% CI; 1.67 (1.19–2.36)). Stratification according to ethnicity did not show significant effects of the Val66Met polymorphism on MDD. Our results suggest that the BDNF Val66Met polymorphism is of greater importance in the development of MDD in men than in women. Future research into gender issues will be of interest.