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

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
PEDIATRICS (Impact Factor: 5.47). 06/2009; 123(5):1344-51. DOI: 10.1542/peds.2008-1892
Source: PubMed


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.
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.
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.
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.
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.

Download full-text


Available from: Pi-Chu Kaylene Lin,
  • Source
    • "Most evidence regarding postnatal effects of intrauterine smoke exposure in humans on subsequent lung function or respiratory morbidity has been derived from epidemiological and physiological studies [Stocks and Dezateux, 2003; Svanes et al. 2004; Moshammer et al. 2006; Palmer et al. 2006; Goksor et al. 2007; Haberg et al. 2007; Wang et al. 2008; Hayatbakhsh et al. 2009; Wenten et al. 2009; Henderson et al. 2010; Hersoug et al. 2010; Schultz et al. 2010; Abbott and Winzer-Serhan, 2012; Neuman et al. 2012]. Prenatal nicotine exposure may predispose to BHR during infancy, especially in those with a maternal history of asthma, with BHR still evident in early adulthood [Goksor et al. 2007]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Diverticulosis is one of the most common gastrointestinal conditions affecting the general population in the Western world. It is estimated that over 2.5 million people are affected by diverticular disease in the United States. The spectrum of clinical manifestations of diverticulosis ranges from asymptomatic diverticulosis to complicated diverticulitis. Treatment for symptomatic diverticular disease is largely based on symptoms. Traditional therapy includes fiber, bowel rest, antibiotics, pain control and surgery for selected cases. This review discusses recent advances in the medical treatment of diverticular disease such as the use of mesalamine, rifaximin and probiotics as our understanding of the disease evolves.
    Therapeutic Advances in Respiratory Disease 02/2013; 7(3). DOI:10.1177/1753465813479428 · 1.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The developmental origins of health and disease (DOHaD) approach has evolved over the past 20 years, and the current hypothesis proposes that fetal adaptations to intrauterine and maternal conditions during development shape structure and function of organs. Here we present a review of some environmental exposures that may trigger fetal maladaptations in these processes, including three examples: exposures to tobacco smoke, antidepressant medication, and folic acid deficits in the food supply. We provide a selected review of current research on the effects of each of these exposures on fetal development and birth outcomes, and use the DOHaD approach to suggest how these exposures may alter long-term outcomes. In the interpretation of this literature, we review the evidence of gene-environment interactions based on evaluation of biological pathways and evidence that some exposures to the fetus may be moderated by maternal and fetal genotypes. Finally, we use the design of the National Children's Study (now in progress) to propose how the DOHaD approach could be used to address questions that have emerged in this area that are relevant to reproductive medicine and subsequent health outcomes.
    Seminars in Reproductive Medicine 10/2009; 27(5):391-402. DOI:10.1055/s-0029-1237427 · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Children exposed to tobacco smoke early in life have a higher risk of wheeze. Individual susceptibility may depend on genetic factors. We studied whether variations in single nucleotide polymorphisms (SNPs) in the TNF, glutathione S transferase P1 (GSTP1) and beta2-adrenoreceptor (ADRB2) genes modify the effect of early maternal smoking on the development of childhood asthma, wheeze and allergic sensitization. In the Swedish prospective birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) (n=4089), data collection included questionnaires to measure tobacco smoke exposure and clinical outcomes up to age 4 and medical examinations with blood sampling for specific IgE measurements and genotyping. We defined early maternal smoking as daily smoking by the mother during pregnancy and/or postnatally. We investigated five TNF, six GSTP1 and three ADRB2 SNPs in 982 selected wheezers and non-wheezers. An interaction with early maternal smoking was found for three TNF SNPs (-857C/T, Intron 1, Intron 3) with respect to early wheeze (up to 2 years of age). For example, the odds ratio (OR) for developing early wheeze related to early maternal smoking was 2.4 [95% confidence interval (CI) 1.6-3.7] in children with a wild-type CC homozygote genotype of the TNF-857 SNP, while no tobacco-related risk was seen in children carrying the rare T allele. A clear dose response was observed in children with the CC genotype, with an OR of 1.3 (95% CI 1.1-1.5) per each additional pack per week smoked by the mother during pregnancy. A suggestive interaction with early maternal smoking was also seen for three GSTP1 SNPs (Intron 5, Intron 6 and Ile105Val) with respect to transient wheeze, but not for ADRB2 and wheeze phenotypes. No effect modifications were observed for allergic sensitization. Our results suggest that the risk of early childhood wheeze associated with early maternal smoking may be modified by TNF and GSTP1 polymorphisms.
    Clinical & Experimental Allergy 03/2010; 40(3):458-67. DOI:10.1111/j.1365-2222.2010.03452.x · 4.77 Impact Factor
Show more