Maternal glutathione S-transferase GSTP1 genotype is a specific predictor of phenotype in children with asthma.

Maternal factors are known to influence the heritability and expression of asthma and atopy. We report the association of maternal, paternal and proband GSTP1 genotype with lung function in 145 Caucasian children with asthma. GSTP1 Val105/Val105 and Ala114/Val114 genotypes in the child were associated with non-significant increases in lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio). Paternal genotype had no influence on lung function in the child. In contrast, maternal GSTP1 Val105/Val105 genotype was significantly associated with offspring lung function and was strongly predictive of FEV1/FVC (Val105/Val105 105.2%, Ile105/Val105 and Ile105/Ile105 97.9% p=0.006) and maternal GSTP1 Ala114/Val114 genotype was associated with significantly higher FEV1 (Ala114/Val114 109.0%, Ala114/Ala114 99.0% p=0.008), and FEV1/FVC ratios (Ala114/Val114 104.1%, Ala114/Ala114 98.2% p=0.04). The associations between maternal GSTP1 Val105/Val105 genotype and FEV1/FVC and maternal GSTP1 Ala114/Val114 genotype and FEV1 remained significant (p=0.003 and p=0.007) after correction for child and maternal atopic status, passive smoke exposure, smoking during pregnancy, individual and paternal GSTP1 genotype and was independent of transmission to the child. These data support the hypothesis that maternal GSTP1 genotype can act as a specific risk factor which has ex utero consequences for children with asthma. As a child's genotype is not independent of maternal genotype, effects seen in candidate gene studies may be due at least in part to this phenomenon.