Perhaps more significantly, iPS-derived neural cells may provide a model to examine between-subject differences in molecular and physiologic responses to acute or chronic alcohol exposure, and in gene function with respect to between-subject genetic variation. Although preliminary, our results suggest that patterns of NMDA mRNA expression change following repeated alcohol treatments vary from subject to subject. Further, increases in expression may be more common in neural cells derived from alcoholic subjects than from non-alcoholics. This finding suggests that heritable traits may render gene expression in the NMDA system more reactive to effects of alcohol in persons predisposed to AD and may thereby contribute to the development of tolerance to the inhibitory effects of alcohol on the NMDA receptor activity. Although the list of genetic markers associated with alcohol dependence is expanding (Edenberg and Foroud, 2006, Enoch et al., 2009, Kimura and Higuchi, 2011), the biological correlates of polymorphisms reported to be associated with alcohol dependence are in large part unknown. iPS cell technologies may provide a powerful tool with which to study the functional effects on neural tissue of alleles identified with alcohol dependence risk.
