Functional tests have also shown that rs16969968, a nonsynonymous SNP (Asp398Asn) in CHRNA5 implicated in GWA studies, lies in the M3-M4 intracellular loop of the receptor and may be involved in receptor trafficking but not receptor expression levels (35). While such studies are encouraging, the functional significance of genetic variation in the CHRNA5-A3-B4 gene cluster is not yet clear.
