A significant association of variants in CHRNA4, which encodes the α4 subunit, with ND has been detected in three independent studies. The first study revealed significant protective effects of two SNPs against ND in Chinese men.35 A second study showed that four SNPs and HAPLOTYPEs that consisted of these SNPs are significantly associated with ND in European and African Americans, but the effects differed as a function of ethnicity or sex.36 A third study reported that two SNPs are significantly associated with the subjective response to smoking.37 Although not all associations have been replicated, two SNPs (rs1044396 and rs2236196) are consistent in two of the three studies. Together, these studies provide evidence that variations in CHRNA4 influence ND.
