The genes that contain multiple clustered nominally-positive SNPs that distinguish successful quitters from those who could not abstain successfully also represent an interesting group. This list of genes includes several that contain SNPs whose allelic frequencies also distinguish nicotine dependent from control individuals. Cadherin 13 is a cell adhesion molecule identified in both comparisons and in the linkage results noted above. Cadherin 13 is glycosyl-phosphatidylinositol (GPI) anchored and likely to be localized to lipid raft membrane domains where it produces homophilic interactions with other CDH 13 molecules and heterophilic interactions with ligands that include adiponectin hexamers and low density lipoproteins [37-40]. Ligand interactions with CDH13 activate signaling pathways including those that alter intracellular Ca2+ and tyrosine kinase, Erk 1/2 kinase, RhoA/ROCK and Rac pathways and NFkB [37-40]. Cadherin 13 can inhibit neurite extension from select neuron populations both as a substratum and as a soluble recombinant protein [41]. Expression is documented in neurons located in interesting human brain regions including frontal cortex, amygdala and ventral midbrain [42].
