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Alpha 5 Nicotinic Receptor Subunit Gene Polymorphisms and Smoking Addiction

Principal Investigator: Alexey Mukhin

Funding Mechanism: National Institutes of Health- Grant

ID number: 1R01DA034862-01

Award Date: 3/15/2013

Institution: Duke University


Recent animal studies of nicotine self-administration have indicated the critical role of the habenula α5 nicotinic receptor subunit in the suppression of excessive nicotine intake. Approximately 60% of smokers carry the risk allele for the non-synonymous coding SNP α5 subunit gene (SNP rs16969968, rs588765), which causes the substitution of an aspartic acid with asparagine and results in decreased function of the nicotinic receptor. This risk allele is associated with number of cigarettes smoked per day, nicotine dependence, and lung cancer. The goal of this project is to assess how smokers with different α5 nicotinic receptor subunit genotypes respond to switching between cigarettes with varied nicotine yields and to nicotine patch application. Specific aims are: (1) to demonstrate that α5 risk allele carriers, relative to controls, have greater increases in nicotine intake after switching to higher nicotine yield cigarettes; (2) to determine if smokers with the α5 risk allele have a lower reduction of nicotine intake from cigarettes while on the nicotine patch than smokers without this allele; and (3) to show that α5 risk allele carriers demonstrate greater smoking compensation after switching to low nicotine yield cigarettes. Two hundred adult cigarette smokers (aged 18-65) will be genotyped for the α5 subunit gene and will complete a 13-week protocol consisting of one screening/evaluation visit, eight laboratory visits, and seven phases of monitored smoking under assigned conditions involving the use of own-brand cigarettes, nicotine patch, and research cigarettes with varying nicotine yields (0.3-1.6 mg). Results from this study will contribute to the understanding of individual differences in vulnerability to tobacco dependence and may inform FDA activities related to product standards addressing nicotine.


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