We’ve known for a while that genes play a role in addiction in general and that nicotine is addictive at least in part because it activates receptors for a chemical called Acetylcholine (ACh) that are found all over the brain and body. Nevertheless, finding the specific mechanism for the genetic predisposition has been difficult.

Some recent large-scale studies undertaken at the University of Colorado and other institutions  around the country have made some very exciting discoveries in this area.  It seems that up to now, researchers were focusing on the most common type of ACh receptor, but that several other types play very important roles in determining how people will respond to nicotine the first time they use it, and how much they’ll be likely to use in that early period. It should be pretty obvious that both there factors can play a huge role in nicotine addiction, and indeed, it seems they do.

So here’s a little breakdown of the findings:

• Initially, research examining the influence of ACh receptor proteins on nicotine addiction focused on the α4 and β2 subunits. These are the most common ACh subunit proteins in the brain. Animal and human imaging studies have shown that ACh receptors consisting of two α4 and three β2 subunits are critical for the rewarding effects of nicotine.
• The new studies focused on genes that code for less common ACh receptor proteins. Researchers have implicated the genes for the α3, α5, and β4 proteins in early initiation of smoking, the transition to dependence, and two smoking-related diseases: lung cancer and peripheral arterial disease.
• Investigators also found that whether or not a person becomes dizzy the first time he tries smoking, as well as his or her risk of addiction, depends in part on the genes for the α6 and β3 proteins.

Taken together, the results suggest that genes for several ACh receptor proteins drive different aspects of the multi-step process of nicotine addiction.

The importance of the first time

Interestingly, the findings regarding first smoking experience seem to suggest that the intensity of it, rather than simply how pleasurable it was, are associated with the likelihood of becoming dependent later on, according to Dr. Ehringer, one of the studies’ lead author. For example, the same people that reported feeling extremely dizzy their first time were more likely to report that they became addicted to nicotine. The genetics analysis supported this same finding.

From trying to becoming addicted

Other studies revealed that additional genetic variations, including those in the the gene for the α3 ACh subunit, the β3 subunit, and the α5 subunit seem to code for the likelihood of being able to quit smoking. The α5 protein, which is present in the brain’s reward area, seems to influence the risk of smoking a pack of cigarettes a day as compared with smoking fewer than 5 cigarettes a day.

Conclusions for smoking addiction

I’ve said it before and I’ll say it again and again – no matter how much we try to ignore it, genetics play a huge role in every aspect of our being, including the likelihood that we will become addicted to a substance. By learning more about the role of specific genes and specific types of receptors, researchers can attempt to uncover possible medications that will help us in treating addiction. Still, I think that the bigger take-home message is this: There are reasons behind the development of addiction that are beyond anyone’s control. Thinking of genetic causes and relating them to morality simply makes no sense.

 Citation:

Lori Whitten (2009). Studies Link Family of Genes to Nicotine Addiction – Genes for protein constituents of nicotinic acetylcholine receptors influence early smoking responses and the likelihood of nicotine dependence. NIDA Notes, 22.