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 Val(105)/Val(105) and Ala(114)/Val(114) 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 Val(105)/Val(105) genotype was significantly associated with offspring lung function and was strongly predictive of FEV1/FVC (Val(105)/Val(105) 105.2%, Ile(105)/Val(105) and Ile(105)/Ile(105) 97.9% p = 0.006) and maternal GSTP1 Ala(114)/Val(114) genotype was associated with significantly higher FEV1 (Ala(114)/Val(114) 109.0%, Ala(114)/Ala(114) 99.0% p = 0.008), and FEV1/FVC ratios (Ala(114)/Val(114) 104.1%, Ala(114)/Ala(114) 98.2% p = 0.04). The associations between maternal GSTP1 Val(105)/Val(105) genotype and FEV1/FVC and maternal GSTP1 Ala(114)/Val(114) 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.