N-acetyltransferase 1 polymorphism increases cotinine levels in Caucasian children exposed to secondhand smoke: the CCAAPS birth cohort

Cotinine is a proxy for secondhand smoke (SHS) exposure. Genetic variation along nicotine and cotinine metabolic pathways may alter the internal cotinine dose, leading to misinterpretations of exposure-health outcome associations. Caucasian children with available SHS exposure and hair cotinine data were genotyped for metabolism-related genes and. SHS-exposed children had 2.4-fold higher hair cotinine (0.14ng/mg±0.22) than unexposed children (0.06ng/mg±0.05, p<0.001). SHS-exposed children carrying the NAT1 minor allele had 2-fold higher hair cotinine (0.18ng/mg for heterozygotes and 0.17ng/mg for homozygotes) compared to major allele homozygotes (0.09ng/mg, p=0.0009), even after adjustment for SHS dose. These findings support that NAT1 has a role in the metabolic pathway of nicotine/cotinine and/or their metabolites. The increased cotinine levels observed for those carrying the minor allele may lead to SHS exposure misclassification in studies utilizing cotinine as a biomarker. Additional studies are required to identify functional SNP(s) in NAT1 and elucidate the biological consequences of the mutation(s).