Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males.

Data from animal studies and from genetic scans in humans suggest that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be involved in the mechanisms underlying substance abuse. The present study tested the hypothesis that the BDNF-gene Val66Met polymorphism is associated with substance abuse. We studied this polymorphism in 103 methamphetamine- and 200 heroin-dependent cases and 122 normal controls. We also considered the association of this polymorphism with age of onset of substance abuse in the heroin-dependent cases. Significant differences in BDNF Val66Met genotype distribution were found between subjects dependent on methamphetamine (P = 0.046) or heroin (P = 0.045) and controls, suggesting that the lower 66Met carrier frequency is associated with substance abuse. Furthermore, in the heroin-dependent group, the Val/Val homozygotes had a later onset of substance abuse compared with the Met allele carriers. The results suggest that the BDNF Val66Met polymorphism or a nearby locus may be involved in the pathogenesis of substance abuse. Our findings support previous genetic scan results showing that BDNF may contribute to substance abuse vulnerability.