Renin-Angiotensin System Genes and Nicotine Dependence

Abstract Animal experiments indicate that dopaminergic signaling is influenced by the brain renin-angiotensin system (RAS); this influence may be an important determinant in the etiology of substance abuse. Although RAS components are genetically determined and genetics has been proposed to play a substantial role in the vulnerability to substance abuse, data that link RAS to substance abuse are sparse in human populations. Most previous studies investigated whether a functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene affected smoking behavior. Their findings argued that ACE-I/D variants played a weak modulatory role in smoking behavior, but they also suggested the intriguing possibility that the role of ACE-I/D polymorphisms in nicotine dependence may differ in the contexts of different diseases and/or conditions. Moreover, ACE-I/D polymorphisms might be more relevant in determining smoking risk in psychiatric disorders compared to other diseases and/or conditions. In this chapter, we discuss these studies and shift our perspective toward future genetic and/or environmental studies that investigate links between RAS components and nicotine dependence.