Contrary to prior reports and in vitro evidence [27], the 3′ UTR conversion that defines the *1B allele is not a significant predictor of variation. However, a synonymous SNP in the first exon, rs1137115 (51A>G), previously reported as associated with gene expression [24], is a significant predictor. The minor allele of rs1137115 (51A) may have a direct effect on function, possibly by reducing gene expression or mRNA stability, or by altering CYP2A6 mRNA splicing. Alternatively, the minor allele may be in linkage disequilibrium with other non-coding polymorphisms that affect expression or splicing of CYP2A6; these could include rs4803381 (−1013A>G) and rs61663607 (−745A>G), although other results argue against them [22]. Lastly, rs1137115 (51A>G) may be in linkage disequilibrium with polymorphisms that affect the activity of adjacent nicotine metabolism genes, i.e. CYP2B6 and CYP2A7. Resolution of this question also has bearing on interpretation of the functional effect of the S29N polymorphism (rs28399435) that defines the *14 allele. As previously reported [24], and supported by our observations, this polymorphism is in complete linkage disequilibrium with the minor allele of rs1137115 (51A). Yet we
