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J Mol Neurosci. 2011 Mar;43(3):524-30. doi: 10.1007/s12031-010-9478-y. Epub 2010 Nov 20.

Association between C-281A and val66met functional polymorphisms of BDNF gene and risk of recurrent major depressive disorder in Polish population.

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Department of Medical Genetics, Medical University of Silesia, Ostrogorska 30 Street, 41-200, Sosnowiec, Poland.


According to neurotrophic hypothesis, brain-derived neurotrophic factor (BDNF) is the potential candidate involved in the pathogenesis of depression. We examined the influence of C-281A (rs28383487) and val66met (rs6265) functional polymorphisms in BDNF gene on vulnerability to major depressive disorder, recurrent (MDD-R), in a Caucasian population. To our knowledge, this is the first case-control study to examine C-281A polymorphism in MDD-R. Genetic studies assessing the relationship between val66met polymorphism and major depression have yielded ambiguous results. We conducted a comparison of allele and genotype frequencies between 116 in-patients with MDD-R and 218 healthy subjects. Analyses were performed for whole groups as well as according to sex. Haplotype analysis was also performed. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for genotyping of single nucleotide polymorphisms (SNPs). C-281A and val66met polymorphisms are in a linkage disequilibrium (LD). This study failed to find an association between C-281A polymorphism with MDD-R, but such an association was found in the case of val66met polymorphism. The val/val genotype was more frequent in depressed individuals compared to the control group, both in total analysis and after stratification by sex. The val allele is connected with a higher risk of MDD-R development in men than in women. Correspondence analysis has shown that the co-presence of genotypes val/val and C/C is connected with a higher risk of MDD-R development (odds ratio [OR]=2.05, p<0.01) compared to other genotype combinations in both analysed SNPs. Haplotype analysis has shown a significantly lower frequency of met-C haplotype in depressed individuals compared to the control group.

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