in our study may be that the previous meta-analyses included a substantial number of former smokers whereas our studies included only current smokers (21). It was previously observed that the influence of CHRNA5-A3-B4 gene variants on self-reported CPD is stronger in the former smokers compared to the current smokers (see Table S7 of Amos et al. study (8)). It is also possible that the lower number of cigarettes smoked per day by light smokers in the current study (mean=7.7) in contrast to the previous meta-analysis (mean ranged from 11.5-15.7) mitigated the expression of the underlining biological impact of the CHRNA5-A3-B4 gene variants on smoking level. However, it is important to note that CPD is a poor marker of tobacco consumption, susceptible to reporting and recalling biases and insensitive to smoking topography. The average cotinine levels, a more objective marker of tobacco consumption, in our study (mean=240 ng/mL, standard deviation=138) were comparable to previously observed in Caucasian and American African heavy smokers (mean≈170 ng/mL) (26). Previous studies in the CHRNA5-A3-B4 field have suggested objective biomarkers are more sensitive than CPD (7). We have previously shown that CHRNA5-A3-B4 variants are significantly associated with cotinine levels in as few as 163 smokers (12).
