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Effects of glutathione-S-transferase M1, T1, and P1 on childhood lung function growth

Frank D Gilliland1, W James Gauderman, Hita Vora

  • 1Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. gillilan@usc.edu

American Journal of Respiratory and Critical Care Medicine
|September 3, 2002
PubMed

Insights

Glutathione-S-transferase (GST) M1 and GSTP1 gene variants impact lung function growth in children. Specific genotypes are linked to slower growth rates, particularly in non-Hispanic white children and those with asthma.

Area of Science:

  • Environmental Health
  • Genetics
  • Pediatric Pulmonology

Background:

  • Genetic variations in glutathione-S-transferase (GST) enzymes, crucial for detoxification, may influence respiratory health.
  • The Children's Health Study provides a unique dataset to examine gene-environment interactions affecting lung development in children.

Purpose of the Study:

  • To investigate the association between glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes and lung function growth in children.
  • To determine if specific GST genotypes modify lung function trajectories over time.
  • To explore potential interactions between GST genotypes, asthma, and lung function growth.

Main Methods:

  • Analysis of lung function growth (FVC, FEV1) over 4 years in 1,940 children using two-level regression models.
  • Genotyping for GSTM1, GSTT1, and GSTP1 codon 105 variants (ile105/val105) from buccal cell DNA.
  • Stratified analyses examining effects by asthma status and ethnicity.

Main Results:

  • GSTM1 null genotype was associated with reduced annual growth rates for FVC and FEV1.
  • Homozygosity for the GSTP1 val105 allele correlated with slower lung function growth compared to ile105 alleles.
  • Children with asthma homozygous for GSTP1 val105 showed significantly larger deficits in lung function growth.
  • Deficits in lung function growth associated with GSTM1 null and GSTP1 val105 were most pronounced in non-Hispanic white children.

Conclusions:

  • GSTM1 and GSTP1 genotypes are significantly associated with lung function growth patterns in school-aged children.
  • These genetic factors may play a role in differential susceptibility to factors affecting lung development.
  • Further research into gene-environment interactions is warranted to understand pediatric respiratory health outcomes.

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