Advances in association of genetic polymorphisms within the dopaminergic
system with nicotine dependence
Abstract
Nicotine is the main compound in cigarettes which leads to smoking
addiction. Nicotine acts on the limbic dopamine reward loop in the
midbrain through binding to nicotinic acetylcholine receptors, promoting
the release of dopamine, resulting in a rewarding effect or
satisfaction. This satisfaction is essential for continued and
compulsive tobacco use, and therefore dopamine plays a crucial role in
nicotine dependence (ND). Numerous studies have identified genetic
polymorphisms of dopaminergic pathways which may influence nicotine
susceptibility and the degree of addiction. Dopamine levels are greatly
influenced by synthesis, storage, release, degradation, and reuptake
related genes, including genes encoding tyrosine hydroxylase (TH),
dopamine decarboxylase (DDC), dopamine transporter (DAT1/SLC6A3),
dopamine receptor (DRD), dopamine 3-hydroxylase (DBH), catechol oxygen
methyltransferase (COMT), and monoamine oxidase (MAO). In this paper, we
review research progress on the effects of polymorphisms in the above
genes on downstream smoking behavior and ND, to provide a theoretical
basis for the elucidation of the genetic mechanism underlying ND and
future personalized treatment for smoking cessation.