In the first report, Feng et al. (2004) identified two synonymous SNPs in exon 5 (rs1044396, rs1044397), which were significantly associated with reduced risk for ND in Chinese men. Li et al. (2005) replicated and extended the association of CHRNA4 with smoking behavior in EAs and AAs, but the association results were not entirely consistent with those published by Feng. For example, rs1044396 showed a significant association with ND in the Chinese male sample but showed no association in the EA or AA samples and rs2236196 showed significant association in AA females but not in Chinese males. More recently, an association study in 5500 Germans showed that rs2236196 was significantly associated with FTND and the “G” allele was associated with a higher risk of nicotine addiction and higher odds of being a smoker (Breitling et al., 2009). The accumulating evidence from genetic association studies plus the additional findings on clinical effects (Hutchison et al., 2007) suggest that rs2236196 could be one of the most promising risk variants for smoking-related behaviors.
