To validate the predictive model, subjects were stratified by gender and smoking status. Parameter estimates based on measurements at 30 min in only females predicted phenotype in male subjects (n=89) with an adjusted R2 of 0.617. Equivalent estimates based on only males predicted phenotype in female subjects (n=100) with an adjusted R2 of 0.758. Parameter estimates based on measurements at 30 min in only non-current smokers predicted phenotype in current smokers (n=102) with an adjusted R2 of 0.703, and equivalent estimates in current smokers (n=86) predicted phenotype in non-current smokers with an adjusted R2 of 0.690. The power of estimates based on each group to predict phenotype in the other also indicates that the relative influence of different CYP2A6 haplotypes do not differ between men and women or smokers and non-current smokers. To further test the stability of the model and determine whether the genotype/phenotype correlation is being dominated by outliers, the analysis was also repeated excluding the three slowest metabolizing subjects. Parameter estimates based on measurements at 30 min in all subjects predicted metabolism in the remaining subjects with an R2 of 0.550.
