NEUROTRANSMITTER RECEPTOR POLYMORPHISM IN NICOTINE ADDICTION

T'Prien C. Stoffer, Lee Nowak, and Eric W. Johnson

Nicotine targets the nicotinic acetylcholine receptor (nAChR), one of the family of ligand-gated ion channels found in the brain and perhaps the most ubiquitous neurotransmitter receptor in the human CNS. The nAChR is composed of 5 subunits arranged in a pentameric configuration forming a membrane spanning ion channel. There are at least 6 different types of subunits that have been identified to date. However, only Alpha and Beta subunits have been seen in the CNS.

This study examines the possibility and frequency of nAChR receptor subunit polymorphism in the general population. Alpha-4, alpha-7, and beta-2 were examined initially because they are most abundant. Primers were designed to amplify exon segments of each specific receptor subunit. Both manual and automated sequencing on the CEQ were performed. Genomic DNA from twenty-one randomly chosen anonymous individuals was used and frequencies of polymorphism for each allele estimated. The hypothesis is that polymorphisms of these receptors exist and play a role in different levels of sensitivity to nicotine. At this point, polymorphisms in exons alpha-4 and beta-2 have not been found in the individuals analyzed. Subsequent sequencing will be performed using a larger panel of random, anonymous genomic DNA and a target panel of DNA isolated from smokers.