Title: N-acetyltransferase 1 polymorphism increases cotinine levels in Caucasian children exposed to secondhand smoke: the CCAAPS birth cohort.
Authors: LeMasters, G K; Khurana Hershey, G K; Sivaprasad, U; Martin, L J; Pilipenko, V; Ericksen, M B; Burkle, J W; Lindsey, M A; Bernstein, D I; Lockey, J E; Gareri, J; Lubetsky, A; Koren, G; Biagini Myers, J M
Published In Pharmacogenomics J, (2015 Apr)
Abstract: 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. SHS-exposed children had 2.4-fold higher hair cotinine (0.14±0.22 ng mg(-1)) than unexposed children (0.06±0.05 ng mg(-1), P<0.001). SHS-exposed children carrying the NAT1 minor allele had twofold higher hair cotinine (0.18 ng mg(-1) for heterozygotes and 0.17 ng mg(-1) for homozygotes) compared with major allele homozygotes (0.09 ng mg(-1), 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 single-nucleotide polymorphism(s) (SNP(s)) in NAT1 and elucidate the biological consequences of the mutation(s).
PubMed ID: 25156213
MeSH Terms: Alleles; Arylamine N-Acetyltransferase/genetics*; Biomarkers/metabolism; Child; Child, Preschool; Cotinine/metabolism*; Female; Genotype; Humans; Infant; Isoenzymes/genetics*; Male; Nicotine/adverse effects; Nicotine/metabolism; Polymorphism, Single Nucleotide/genetics*; Smoking/adverse effects; Smoking/metabolism; Tobacco Smoke Pollution; White People/genetics*