Background: Polymorphisms in the brain-derived neurotrophic factor (BDNF) val66met and serotonin transporter gene-linked promoter region (5-HTTLPR) are associated with alterations in mood and BDNF protein, but the effects of two genetic variations on the serum level of BDNF is unclear. Therefore, we sought to explore the effects of two polymorphisms on serum levels of BDNF in healthy subjects.
Methods: One hundred healthy Korean subjects were genotyped. Serum levels of BDNF were measured with enzyme-linked immunoassay, and factors (sex, age, body mass index, alcohol and smoking) that can affect BDNF level were evaluated. The effects of these two genetic variations on serum levels of BDNF were tested using an analysis of covariance.
Results: We found that serum levels of BDNF were significantly affected by the factor 'genotype' (met carrier vs. val homozygote) (F=4.618, p=0.034) and (s homozygote vs. l carrier) (F=3.965, p=0.049), respectively. Moreover, subjects with s homozygosity at the 5-HTTLPR and BDNF met carriers (16.2±7.9 ng/ml) had lower serum levels of BDNF as compared with those with l carriers of the 5-HTTLPR in combination with BDNF val homozygosity (21.7±4.4 g/ml) (p=0.024).
Limitations: A larger study will be needed to confirm this additive effect of both risk genotypes.
Conclusions: In this study, we report for the first time that healthy subjects who were homozygous for s at 5HTTLPR and the met allele of the BDNF val66met polymorphism displayed significantly lower serum levels of BDNF. Our findings might contribute to a better understanding of the effect of BDNF and 5-HTTLPR gene on serum BDNF level in humans.
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