Effects of glutathione S-transferase M1, T1 and P1 on lung function in asthmatic families

Clin Exp Allergy. 2005 Sep;35(9):1155-61. doi: 10.1111/j.1365-2222.2005.02313.x.

Abstract

Rationale: Previous data have suggested that glutathione-S-transferase (GST) genotypes are important in determining the rate of lung function growth in childhood. This effect was most marked in Caucasian children with asthma.

Objectives: We investigated the association of lung function with GSTM1, GSTP1 and GSTT1 genotypes in Caucasian families with asthma.

Methods: Four hundred and eighteen children and 316 parents from 224 Caucasian families were recruited via a child with asthma, the proband. Associations between lung function and GST genotype were determined using multilevel models.

Results: There were no observed associations between lung function and GST genotype in parents. However, in the children, the GSTP1 val(105)/val(105) and GSTM1 null genotypes were associated with significantly higher forced expiratory volume in 1 s (FEV(1)) and FVC values as percentage of predicted. This effect was not statistically significant in the probands but was marked in their siblings in whom GSTP1 val(105)/val(105) was associated with 9.4% higher FEV(1) and 10.7% higher FVC (P=0.005 and 0.001, respectively). The GSTM1 null genotype was associated with a 6.7% higher FEV(1) and 4.1% higher FVC (P=0.003 and 0.063, respectively). These effects remained significant after correcting for the confounders of individual atopic status, tobacco smoke exposure and familial aggregation of lung function values.

Conclusions: GSTM1 and GSTP1 genotypes are important determinants of lung function in childhood. The smaller differences seen in probands are predicted by a simple model in which more rapid decline in lung function is seen in these individuals.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asthma / enzymology*
  • Asthma / genetics
  • Asthma / physiopathology
  • Child
  • England
  • European Continental Ancestry Group
  • Female
  • Forced Expiratory Volume
  • Genotype
  • Glutathione Transferase / genetics*
  • Homozygote
  • Humans
  • Isoenzymes / genetics*
  • Linear Models
  • Lung / enzymology*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Parents
  • Siblings
  • Vital Capacity

Substances

  • Isoenzymes
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1