In human studies, SNPs or haplotypes of the CHRNA4 gene have been associated with nicotine dependence in family-based analyses (Feng et al. 2004; Li et al. 2005), a large-scale genetic association study (Breitling et al. 2009b), and in a study evaluating unrelated European Americans and African-Americans (Han et al. 2011). GWAS studies have not identified the CHRNA4 gene as a risk locus for smoking behavior phenotypes (Berrettini et al. 2008; Caporaso et al. 2009; Liu et al. 2009, 2010; TAG 2010; Thorgeirsson et al. 2010; Thorgeirsson and Stefansson 2008; Vink et al. 2009). However, in a candidate gene study, the rs2236196 polymorphism was associated with smoking cessation outcomes (Hutchison et al. 2007). Specifically, this SNP was associated with self-reported abstinence for 7 days before the end of 8 weeks of treatment with either transdermal nicotine patch or nicotine nasal spray. An independent sample of smokers with the rs2236196 polymorphism reported increased sensitivity to the acute effects of smoking after 8 h of abstinence and subjects treated with nasal spray maintained treatment gains at 6 months follow-up (Hutchison et al. 2007).
