Increase in Serum Brain-Derived Neurotrophic Factor in Met Allele Carriers of the BDNF Val66Met Polymorphism Is Specific to Males

Background: Association studies of the Val66Met polymorphism and serum brain-derived neurotrophic factor (BDNF) levels have yielded conflicting results. Recently, sex-specific differences in BDNF levels were demonstrated. As these might explain the reported inconsistencies, we tested sex interactions with the Val66Met genotype on serum BDNF level. Methods: Participants (n = 548, age range 50-72 years; mean 62.8 +/- 5.4 years, 267 males) were tested for rs6265 genotype and serum BDNF levels [Hardy-Weinberg equilibrium (HWE), p = 0.04]. A regression analysis with BDNF level as the dependent variable and BDNF Val66Met genotype as an independent variable was used to test the sex interaction corrected for age, smoking and depressive symptoms. Subsequently, we examined the effect of genotype on BDNF levels stratified for sex. Results: We found a significant interaction between sex and genotype on BDNF levels (p = 0.02). Male Met carriers had significantly higher BDNF levels than Val/Val homozygotes (beta = 0.17, p = 0.013), while in females no effect of Val66Met genotype was found (beta = -0.07, p = 0.28). Conclusion: Our findings may partly explain the inconsistent findings of earlier studies where results were influenced by male-female ratios. Replication is warranted, however, as our sample was not in HWE.