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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 710-716, (2002)
© 2002 American Thoracic Society

Original Article

Effects of Glutathione-S-Transferase M1, T1, and P1 on Childhood Lung Function Growth

Frank D. Gilliland, W. James Gauderman, Hita Vora, Edward Rappaport and Louis Dubeau

Departments of Preventive Medicine and Pathology, University of Southern California Keck School of Medicine, Los Angeles, California

Correspondence and requests for reprints should be addressed to Frank Gilliland, Department of Preventive Medicine, University of Southern California Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, CA 90033. E-mail: gillilan{at}usc.edu

The effects of glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes on lung function growth were investigated in 1,940 children enrolled in the Children's Health Study as fourth graders (aged 8–11 years) in two cohorts during 1993 and 1996 and were followed annually over a 4-year period. Genotypes for GSTM1 and GSTT1 and GSTP1 codon 105 variants (ile105 and val105) were determined using DNA from buccal cell specimens. We used two-level regression models to estimate the effects of GSTM1, GSTT1, and GSTP1 genotypes on the adjusted annual average lung function growth. GSTM1 null was associated with deficits in annual growth rates for FVC (-0.21%; 95% confidence interval [CI], -0.40, -0.03) and FEV1 (-0.27%; 95% CI, -0.50, -0.04). Children who were homozygous for the GSTP1 val105 allele had slower lung function growth (FVC -0.35%; 95% CI, -0.62, -0.07; and FEV1 -0.34%; 95% CI, -0.68, 0.00) than children with one or more ile105 alleles. Children with asthma who were homozygous for the GSTP1 val105 allele had substantially larger deficits in FVC, FEV1, and maximal mid-expiratory flow than children without asthma. The deficits in FVC and FEV1 growth associated with both GSTM1 null and the GSTP1 val105 allele were largest and were statistically significant in non-Hispanic white children. We conclude that GSTM1 and GSTP1 genotypes are associated with lung function growth in school children.

Key Words: glutathione-S-transferase • FEV • children • polymorphism • growth




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