title: N-acetyltransferase 1 polymorphism increases cotinine levels in Caucasian children exposed to secondhand smoke: the CCAAPS birth cohort.
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).
authors.affiliation: Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: LeMasters
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: Khurana Hershey
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: U
authors.initials: U
authors.lastname: Sivaprasad
authors.affiliation: 1] Division of Human Genetics, Cinc innati Children's Hospital Medical Center, Cincinnati, OH, USA [2] Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Martin
authors.affiliation: Division of Human Genetics, Cinc innati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: V
authors.initials: V
authors.lastname: Pilipenko
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Ericksen
authors.affiliation: Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Burkle
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Lindsey
authors.affiliation: Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: D I
authors.initials: DI
authors.lastname: Bernstein
authors.affiliation: Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Lockey
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Gareri
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lubetsky
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Koren
authors.affiliation: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Biagini Myers
mesh_terms: D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003367:Cotinine / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D009538:Nicotine / Q000009:adverse effects / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism; D014028:Tobacco Smoke Pollution; D044465:White People / Q000235:genetics*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D014028:Tobacco Smoke Pollution; D009538:Nicotine; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; D003367:Cotinine