Published online April 27, 2009
PEDIATRICS Vol. 123 No. 5 May 2009, pp. 1344-1351 (doi:10.1542/peds.2008-1892)
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ARTICLE

In Utero Smoke Exposure, Glutathione S-Transferase P1 Haplotypes, and Respiratory Illness–Related Absence Among Schoolchildren

Madé Wenten, MS, MPH, Yu-Fen Li, PhD, MPH, Pi-Chu Lin, MS, W. James Gauderman, PhD, Kiros Berhane, PhD, Edward Avol, MS and Frank D. Gilliland, MD, PhD

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

BACKGROUND. The GSTP1 Ile105Val variant and secondhand tobacco smoke exposure have been independently associated with acute respiratory illness; however, susceptibility to in utero and secondhand tobacco smoke has yet to be examined in relation to variation across the GSTP1 locus.

OBJECTIVE. The purpose of this work was to determine whether variation across the GSTP1 locus is associated with respiratory illness–related school absences and to determine whether this relationship varies by in utero and secondhand tobacco smoke exposure.

METHODS. Tobacco smoke exposure status, incident respiratory-related school absence records, and DNA samples was ascertained for 1132 Hispanic and non-Hispanic white elementary school children as part of the Children's Health Study.

RESULTS. Four GSTP1 single-nucleotide polymorphisms were selected that accounted for 93% of the variation across the locus. Individual single-nucleotide polymorphism analyses showed a protective effect for the minor alleles in single-nucleotide polymorphisms 1 (rs6591255), 3 (GSTP1 Ile105Val: rs1695), and 4 (rs749174) for respiratory illness. The haplotype, which includes a minor allele for single-nucleotide polymorphisms 1, 3, and 4 (h1011), was associated with a decreased risk of respiratory illness. The protective effect of GSTP1 variants was lost among individuals exposed to in utero and secondhand tobacco smoke.

CONCLUSIONS. A common GSTP1 haplotype, which includes the functional Ile105Val polymorphism, was associated with respiratory-related school absences. The protection afforded by this haplotype was lost in children exposed to involuntary tobacco smoke. The paradigm of loss of genetic protection among those exposed to tobacco smoke has clinical and public health implications that warrant broader consideration in research and practice.

Key Words: respiratory illness • GSTP1 • haplotype • in utero smoke • secondhand smoke

Abbreviations: SHS—secondhand smoke • GSTP1—glutathione S-transferase P1 • APAS—Air Pollution and Absence Study • SNP—single-nucleotide polymorphism • LD—linkage disequilibrium • CI—confidence interval • RR—relative risk • hGSTP1-1—human GSTP1-1

Accepted Sep 2, 2008.


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