GENETICS OF NICOTINE DEPENDENCE

Abstract

Nicotine dependence is a disorder of the use of nicotine, which is found in tobacco smoke. A characteristic feature of this disorder is a strong internal urge to smoke, which is manifested in the deterioration of the ability to control it, increasing the priority of smoking over other types of activities, and in regular smoking, despite the harm to health or other negative consequences. After stopping or reducing the use of nicotine, withdrawal occurs, which forces one to return to smoking or turn to the use of pharmacologically similar substances. According to the World Health Organization, 36.7% of men and 7.8% of women smoke, causing more than 8.7 million deaths annually. Smoking prevalence varies greatly by race and culture, suggesting that nicotine dependence has a biological basis. Numerous twin studies have shown that genetic and environmental factors play a significant and roughly equal role in determining smoking dependence. The results of these studies also indicate that genetic and environmental factors differently determine the nature of smoking dependence in men and women. This indicates that different strategies for the prevention and treatment of tobacco dependence are needed for men and women.
 Currently, 44 candidate genes for nicotine dependence meet the significance criteria, which are involved in the functioning of a number of neurotransmitter systems (dopaminergic, GABA-ergic, serotonergic, glutamatergic, cholinergic), or are genes of subunits of the nicotine receptor, nicotine metabolism, signaling pathway of mitogen-activated protein kinase, etc. Currently, the most studied of them are the DRD2 gene (dopaminergic system), the CHRNA5/CHRNA3/CHRNB4 nicotinic receptor subunit gene cluster, and the CYP2A6/CYP2B6 nicotine metabolism gene cluster.
 In general, significant progress has been made in the study of the genetic mechanisms of nicotine dependence, but much remains unknown. Significant further efforts are needed not only to determine which genetic variants are reliably involved in this mental disorder and which mechanisms of action, but also to develop technologies to use these scientific advances to prevent and treat lifethreatening nicotine dependence.