Mouse Anti Human Glutathione S-transferase Mu1 Hybridoma [DQUD-HTUNv2-8]

Background: Autism spectrum disorders (ASD) are complex psychiatric disorders, with gene environment interaction being in the basis of their etiology. The association of perinatal complications and ASD is well established. Recent findings suggested that oxidative stress and polymorphism in genes encoding antioxidant enzymes might be involved in the development of ASD. Glutathione transferases (GSTs) have an important role in the antioxidant defense system. We aimed to establish whether the predictive effects of prenatal and perinatal complications (as possible oxidative stress inducers) on ASD risk are dependent on GST polymorphisms. Methods: The study included 113 ASD cases and 114 age- and sex group-matched healthy controls. All participants were genotyped for GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms. The questionnaire regarding prenatal and perinatal risk factors and complications was administered for all the subjects in the study. Results: The evaluated perinatal complications as a group significantly increased the risk of ASD [odds ratio (OR) = 9.415; p = 0.0001, as well as individual perinatal complications, such as prematurity (OR = 11.42; p = 0.001), neonatal jaundice (OR = 8.774; p = 0.000), respiratory distress syndrome (OR = 4.835; p = 0.047), and the use of any medication during pregnancy (OR = 2.413; p = 0.03). In logistic regression model, adding GST genotypes did not modify the significant effects found for prematurity and neonatal jaundice as risk factors in ASD. However, there was a significant interaction of GST genotype with medication use during pregnancy and the use of tocolytics during pregnancy, which was predictive of ASD risk only in carriers of GSTM1 -null, as opposed to carriers of GSTM1-active genotype. Conclusion: Specific perinatal complications may be significant risk factors for ASD. GSTM1 genotype may serve as a moderator of the effect of some prenatal factors on the risk of ASD such as using medication during pregnancy. It may be speculated that different oxidative stress-related genetic and environmental factors could lead to development of ASD. Apart from etiological mechanisms, possible therapeutic implications in ASD are also discussed.

Objectives To investigate the association between particulate matter with an aerodynamic diameter of less than 2.5 mu m (PM2.5) exposure during each trimester of pregnancy and development of lower respiratory tract infections (LRTIs) during the first 3 years of life and whether GSTM1 gene polymorphisms modify these effects. Methods This study included 1,180 mother-child pairs from the Cohort for Childhood Origin of Asthma and allergic diseases. The PM2.5 levels during pregnancy were estimated by residential address using land-use regression models based on a national monitoring system. A diagnosis of LRTIs was based on a parental report of a physician's diagnosis. Real-time polymerase chain reaction was used for GSTM1 genotyping. Results Higher PM2.5 exposure during the third trimester was associated with LRTIs at 1 year of age (aRR, 1.06; 95% CI, 1.00-1.13). This result did not change after adjusting for PM2.5 exposures during the first and second trimesters (aRR, 1.06; 95% CI, 0.99-1.13). This association was significant after adjusting for PM2.5 exposures during first year of age (aRR, 1.08; 95% CI, 1.02-1.15) and exposures to NO2 and ozone at the third trimester (aRR, 1.07; 95% CI, 1.00-1.16). In addition, PM2.5 exposure during the third trimester increased the risk of LRTIs at 1 year of age in cases with the GSTM1 null genotype (aRR, 1.26; 95% CI, 1.01-1.57; P for interaction .20). Conclusion Higher PM2.5 exposure during the third trimester of pregnancy may increase the susceptibility to LRTIs at 1 year of age. This effect is modified by GSTM1 gene polymorphisms.