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Effects of Environmental Tobacco Smoke and CYP2A6 and GSTP1 Exposure on Childhood Wheeze

Biagini Myers, Jocelyn Marie
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212161341

Abstract Details

2008, PhD, University of Cincinnati, Medicine : Epidemiology (Environmental Health).
Exposure to environmental tobacco smoke (ETS) is associated with onset of wheeze in children. There may be genetically at risk subgroups with an inability to metabolize components of ETS exposure components or have increased susceptibility to lung injury. Cotinine, the predominate metabolite of nicotine, is metabolized by the cytochrome p450 2A6 gene (CYP2A6). Polymorphisms in this gene have been shown to cause problems in nicotine metabolism resulting in decreased cotinine formation. Children with variant CYP2A6 alleles may have decreased cotinine values even though they have similar exposure as wild-type children. The GSTP1 gene produces the predominant detoxifying enzyme of reactive oxygen species (ROS) in the lung. A variant in this gene causes a decrease in ROS detoxification, which can lead to oxidative stress and lung injury. Children born to atopic parents were genotyped for four variants of the CYP2A6 gene and one GSTP1 variant. Hair samples were analyzed for nicotine and cotinine. Parents reported the number of cigarettes smoked by each resident in the home, number of hours around smoke per day, and ETS exposure in the car. Parents were queried yearly about their child’s wheezing history. Recurrent wheeze was defined as two or more episodes in the past 12 months, and persistent wheeze was defined as recurrent wheeze at ages two and three. In contrast to other studies, African-American parents reported significantly higher ETS exposure, 50% versus 30% for Caucasians (p<0.01). There was a 15% decrease in mean cotinine level among African-Americans with the CYP2A6*9 variant (p=0.1). When cotinine level was dichotomized into high (upper 33%) and low, children with high cotinine and any CYP2A6 variant had increased prevalence of recurrent and persistent wheeze. Among subjects with high cotinine levels, the GSTP1 variant allele was associated with a significantly decreased prevalence of recurrent wheeze (p=0.03). These findings may indicate that African Americans have increased ETS exposure compared to Caucasians, and this may partially explain the increased nicotine and cotinine levels among this group. Without understanding the relationship of CYP2A6 and GSTP1 and cotinine levels, the true impact of ETS on childhood wheeze can not accurately be assessed.
Grace LeMasters, PhD (Committee Chair)
Ranjan Deka, PhD (Committee Member)
Gurjit K. Khurana Hershey, MD, PhD (Committee Member)
Linda Levin, PhD (Committee Member)
112 p.
Epidemiology
ETS; CYP2A6; GSTP1; child; wheeze

Recommended Citations

Citations

  • Biagini Myers, J. M. (2008). Effects of Environmental Tobacco Smoke and CYP2A6 and GSTP1 Exposure on Childhood Wheeze [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212161341

    APA Style (7th edition)

  • Biagini Myers, Jocelyn. Effects of Environmental Tobacco Smoke and CYP2A6 and GSTP1 Exposure on Childhood Wheeze. 2008. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212161341.

    MLA Style (8th edition)

  • Biagini Myers, Jocelyn. "Effects of Environmental Tobacco Smoke and CYP2A6 and GSTP1 Exposure on Childhood Wheeze." Doctoral dissertation, University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1212161341

    Chicago Manual of Style (17th edition)

ucin1212161341
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© 2008, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.