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

The Pharmacogenomics Journal volume 15, pages 189–195 (2015)Cite this article

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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).

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Acknowledgements

We thank the clinic staff for their efforts in study coordination, recruitment, data management and data collection. We also thank all of the CCAAPS families for their time and commitment. This work was supported by the National Institute for Environmental Health Sciences grants R01-ES011170 and P30-ES006096.

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Authors and Affiliations

  1. Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA

    G K LeMasters, J W Burkle & J E Lockey

  2. Division of Asthma Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    G K Khurana Hershey, U Sivaprasad, M B Ericksen, M A Lindsey & J M Biagini Myers

  3. Division of Human Genetics, Cinc innati Children’s Hospital Medical Center, Cincinnati, OH, USA

    L J Martin & V Pilipenko

  4. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    L J Martin

  5. Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    D I Bernstein

  6. Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada

    J Gareri, A Lubetsky & G Koren

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  1. G K LeMasters
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  14. J M Biagini Myers
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Correspondence to J M Biagini Myers.

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LeMasters, G., Khurana Hershey, G., Sivaprasad, U. et al. N-acetyltransferase 1 polymorphism increases cotinine levels in Caucasian children exposed to secondhand smoke: the CCAAPS birth cohort. Pharmacogenomics J 15, 189–195 (2015). https://doi.org/10.1038/tpj.2014.44

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  • DOI: https://doi.org/10.1038/tpj.2014.44

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