The protective rs9829896-C allele was also associated with increased OPRM1 gene expression. The OPRM1 gene has long been suspected to influence susceptibility to drug addiction, given that the protein encoded by OPRM1 is a principal target of natural and synthetic opioids. Our observed pattern for OPRM1 expression is consistent with prior reports showing lower OPRM1 expression levels in putamen(Sillivan et al., 2013) and frontal cortex(Ferrer-Alcon et al., 2004) of heroin abusers compared to normal controls. Down-regulation of OPRM1 may play a role in increasing risk of heroin abuse, by depriving the opioid system of a key compensatory response to heroin exposure.(Oertel et al., 2012) In contrast, up-regulation of OPRM1 may lead to decreased risk of heroin and other drug abuse, as suggested by the trans-regulatory effect of rs9829896-C.
