GSTM1 Null, GSTT1 Null Gene and Low Erythrocyte GST Activity as Risk Factor of Autism Spectrum Disorder

Abstract

Low plasma total glutathione (tGSH) levels, elevated levels of oxidized glutathione(GSSG) and low ratios of tGSH to GSSG in autism was reported. Glutathione S- transferases (GST) are antioxidant enzymes that play important role in cellular detoxification and the excretion of environmental pollutants including heavy metals. At least seven distinct classes have been identified : alpha (α), mu (µ), pi (π), sigma (σ), theta (θ), kappa (κ), and zeta (ξ). Glutathione S-transferase mu (GSTM1) and Glutathione S-transferase theta (GSTT1) are known to be highly polymorphic. Homozygous deletions of these genes result in lack of enzyme activity and impaired the ability to excrete metals including mercury. Combined effects of mercury (Hg) accumulation coupled with decreased levels of antioxidants (low glutathione and antioxidant enzymes) contribute to the phenotypic presentation of Autism Spectrum Disorder (ASD). Association of GSTM1 null genotype with autism has been reported. Therefore the preliminary study was performed to investigate the role of GSTM1 and GSTT1 polymorphism as risk factor of ASD associated with GST activity and phenotype expression. No significant differences were found in frequencies of GSTM1 null,GSTT1 null and combination both genotype between ASD patients and controls. However the mean erythrocyte GST activity in ASD is significantly decreased compared with controls (p=0.043). Whereas, in severely autistic, mean erythrocyte GST activity lower than mild to moderately autistic,but there was no statistically significance. Further investigations are needed with increased sample size,multiple GST genes and GST activity determination, to find out gene susceptibility of ASD and factors that contribute to the phenotype expression of ASD. Keywords: GSTM1;GSTT1;polymorphism: Glutathione S-transferase; erythrocyte; Autism spectrum disorder