Second, genetic variation that modifies noxious responses to nicotine and thereby influences vulnerability to tobacco dependence, in particular variation in the CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor (nAChR) subunit gene cluster, will be discussed.
Indeed, genetic variation in the CHRNA5-CHRNA3-CHRNB4 gene cluster, encoding the α5, α3, and β4 nAChR subunits, respectively, has been shown to increase vulnerability to tobacco dependence and smoking-associated diseases including lung cancer.
Recent human genetic studies also imply that tobacco dependence is affected by polymorphisms in the alpha3/alpha5 subunits of the nAChR (CHRNA3/CHRNA5) gene cluster.