The 5′ portions of the PPP3CA gene harbor haplotypes that display nominally significant association with polysubstance abuse vulnerability in an African–American poly-substance abuse versus control comparison. The evidence is consistent with modest, polygenic contributions from variants at the PPP3CA locus in addiction. Nevertheless, roles for variants in levels of calcineurin expression in reward- and memory-related phenotypes are well documented in animal model studies (Biala et al., 2005; Gerdjikov and Beninger, 2005; Mansuy et al., 1998). Data in the present report supports prior observations of altered PPP3CA expression in postmortem samples from AD brains. The present haplotype-specific expression data, based on 5′ UTR markers, provides a direct link between association data and prior data that describes behavioral effects of altered PPP3CA expression and/or calcineurin activities.
