Several studies have examined the relationship between heroin dependence and BDNF function and rs6265 SNP in the BDNF gene that codes for a valine (Val) to methionine (Met) substitution in the protein’s pro-domain [89-91]. These studies reported impaired depolarization-dependent secretion of BDNF in neuronal cells [90]. It was also observed that valine carriers had a higher level of central BDNF and experienced more intense euphoric effects than methionine carriers [90]. In a study by Cheng et al. [91] that investigated methamphetamine and heroin-dependent Chinese men, the genotype distribution was significantly different in the methamphetamine (P=0.046) and heroin-dependent groups (P=0.045) compared to the control group. The BDNF rs6265 SNP also had an effect on the age of onset of substance abuse in 160 heroin-dependent cases, with the mean age of onset of 20.8 ± 5.1 years for subjects with a heterozygous genotype, which is significantly lower than both homozygous groups (21.2 ± 8.1 and 23.8 ± 7.5 for the Met/Met and Val/Val homozygous groups, respectively) (p = 0.048) [91]. Another investigation of the association between BDNF rs6265 SNP and heroin dependence
