Genetic regulation of platelet-derived BDNF by rs11030119: discrepancy between circulating levels and hemostatic...

Brain-Derived Neurotrophic Factor (BDNF), highly enriched in platelets, contributes to vascular integrity and thrombotic responses. The rs11030119 variant, located in a BDNF intronic enhancer, has been linked to stroke recovery, but its influence on peripheral BDNF dynamics and hemostasis remains unexplored. In this study, we aimed to understand the impact of rs11030119 on circulating levels of BDNF, and its subsequent effects on thrombus formation. Twenty-six healthy individuals homozygous for either the GG or AA genotype of rs11030119 were matched for age and sex. BDNF and proBDNF levels were quantified in serum, plasma, and platelets. Platelet aggregation, ATP secretion, thrombin generation, and clot firmness were assessed. Washed platelets were also tested with recombinant BDNF. AA carriers displayed significantly lower plasma and serum BDNF levels and diminished BDNF release upon activation, despite comparable platelet BDNF content. The expression of its receptor, TrkB, on the platelet surface was also reduced in AA carriers. However, platelet reactivity, thrombin generation, and viscoelastic clot properties were preserved across genotypes. In conclusion, rs11030119 modulates circulating and platelet-releasable BDNF without impairing hemostatic function, suggesting that BDNF bioavailability may not directly correlate with thrombotic potential. These findings uncover a novel genetic mechanism controlling platelet-derived neurotrophin output.