Association Between C-281A and Val66met Functional Polymorphisms of BDNF Gene and Risk of Recurrent Major Depressive Disorder in Polish Population

Author： Suchanek Renata Owczarek Aleksander Kowalczyk Małgorzata Kucia Krzysztof Kowalski Jan

Publisher： Humana Press, Inc

ISSN： 0895-8696

Source： Journal of Molecular Neuroscience, Vol.43, Iss.3, 2011-03, pp. : 524-530

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Abstract

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.