of the polypeptide chain), resulting in a substitution of a negatively charged residue within the M3–M4 intracellular loop, a region thought to be involved in receptor trafficking. A recent function study (Bierut and others 2008) showed that the variant forms of the α5 subunit alter receptor function without affecting expression. In consideration of the extensive LD within this region, a resequencing effort is needed to address this issue. Second, it is necessary to determine if the CHRNA5/A3/B4 cluster also plays a significant role in the etiology of ND and lung cancer in other ethnic populations, such as those with Asian, African, and Hispanic origins, given that most participants to date have been of European descent, the current study being a notable exception. From information from International HapMap project and from the current study, we know LD structures differ greatly across ethnicities. Thus, it is important to determine if the association between this region and both lung cancer and ND exists, and whether the same or different functional variants are responsible (Briollais and others 2007).
