[Heritability and candidate genes in tobacco use]

Abstract

HERITABILITY INDICATORS: Genetic studies of tobacco use can be useful to understand the physiopathology of nicotine dependence and potentially to prevent it. Twin and adoption studies have clearly shown the role of genetic factors in tobacco use at different stages. Genetic factors account for 55% (range: 11-84%) of the smoking initiation and 61% (range: 52-71%) for persistence. Age at onset and intensity of smoking are also influenced by genetic factors. Estimation of the heritability of initiation/persistence of smoking varies by gender. It is estimated as 66%/61% for women and 49%/61% for men respectively. In adolescent twin studies, heritability estimated the liability of lifetime or current use of tobacco to be more than 80%, while the heritability for initiation being between 11% and 59%. Heavy smoking is also influenced by genetic factors, especially when patients are co-abusing alcohol or coffee. Genetics findings - Advances in molecular genetics identified different candidate genes for tobacco use mainly involving neurotransmission of neuromodulators. Because of the brain reward effects of nicotine on the mesolimbic system, the genes involved in the dopaminergic transmission receive specific attention. Genetic polymorphisms of the dopamine D1, D2, D4 and D5 receptors, dopamine transporter (DAT1) and dopamine B-hydroxylase (DBH) have been associated at least once with clinical aspects of tobacco use (initiation, dependence and intensity) and temperament traits as novelty seeking, the latter being lower in smokers and thus considered as a vulnerable marker in accordance with the reinforcement effect of nicotine. Regarding interaction between nicotine use and anxiety and depression, the gene encoding for the serotonin transporter (5-HTT) may constitute a candidate gene. Because of interindividual bioavailability of nicotine, genetic polymorphisms of metabolism enzymes have also been analysed. Some variants of the cytochrome P450 seem to be more frequent among dependent smokers than controls or ever smokers (CYP2A6) and heavier smokers (CYP2D6). Genetic research might be suitable for a therapeutic approach and identify subjects at high risk for nicotine dependence.