GSTM1 polymorphisms modify the effect of maternal smoking during pregnancy on cognitive functioning in preschoolers

Abstract

Maternal smoking during pregnancy is associated with cognitive deficits in children. Parental factors are proposed as an explanatory. We studied the influence of GSTM1 and GSTT1 polymorphisms on the cognition effects induced by active maternal smoking during pregnancy. Children (n = 384) from a prospective population-based birth cohort were assessed at 4 years. The McCarthy Scales of Children's Abilities (MCSA) was administrated. Maternal smoking was measured by questionnaire. Genotyping was conducted for null alleles from GSTM1 and GSTT1. Multivariable linear regression models were used to examine the association between active maternal smoking during pregnancy and MCSA outcomes by GSTM1 and GSTT1 genotypes. Maternal smoking during pregnancy (reporting, yes) was inversely associated with global cognitive score among children having null allele for GSTM1 (beta = -4.73, 95% CI -9.45 to -0.02); but not among children with present allele (beta = -1.04, 95% CI -7.88 to 5.81) (P for interaction 0.089). The interaction remained after adjusting by post-natal maternal smoking (P = 0.081). The effect was stronger for perceptual-performance (beta = -3.68, 95% CI -8.39 to 1.03; P for interaction 0.087), quantitative (beta = -7.00, 95% CI -17.39 to 3.39; P for interaction 0.048), verbal (beta = -3.63, 95% CI -8.43 to 1.17; P for interaction 0.264) and executive function (beta = -4.87, 95% CI -9.55 to -0.20; P for interaction 0.127). No interaction was found for GSTT1. GSTM1 deficiency increases the adverse effects of active maternal smoking during pregnancy on cognition in preschoolers, suggesting a biological interaction between child metabolic genes and tobacco smoke components in detoxification process during foetal neurodevelopment.