Objective: Autism is a neurodevelopmental disorder characterized by impairments and abnormalities in verbal and non-verbal communication and socialization alongside with restricted-stereotyped interests and behaviors. Several factors have been implicated in the etiology of autism, including genetic, environmental and autoimmune factors however the underlying etiology of autism is unknown. There is some evidence that free oxygen radicals play an important role in the pathophysiology of neuropsychiatric disorders, including autism. The aim of this study is to investigate Mn-Superoxide Dismutase, an important enzyme in anti-oxidant defense mechanisms, gene polymorphism in autism spectrum disorders (ASD).
Method: Subjects in this study were children and adolescents aged 2-18 years old, who were referred and followed up with diagnosis of DSM-IV ASD in Istanbul Faculty of Medicine, Child and Adolescent Psychiatry Department. Childhood Autism Rating Scale (CARS) was used to assess the severity of autism symptoms. 10 cc blood sample of affected child and biological mother and father trios were taken into sterile test tube with EDTA for DNA isolation. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and agarose gel electrophoresis were carried out to assess Mn-Superoxide Dismutase gene polymorphism in DNA samples. Genetic analysis was conducted in Istanbul University, Institute of Experimental Medicine (DETAE), and Molecular Medicine Department. Family based approaches like transmission disequilibrium test (TDT) and haplotype-relative-risk (HRR) were used in data analysis. Correlation between inherited alleles and quantitative analysis scores like CARS and IQ , and age of mother was investigated using ANOVA.
Results: 101 subjects (16 females, 15,8%; 85 males, 84,4%) with diagnosis of ASD and their biological parents, a total of 303 subjects, were included in the study. We found significant association between Mn-SOD gene and ASD (p: 0, 0001) (X2:29,438). There was no correlation between inherited alleles, quantitative analysis results like CARS score, IQ score, and age of mother as revealed by ANOVA.
Conclusion: The findings of this study suggest that Mn-SOD might appear to be a viable candidate gene for the pathogenesis of autism and have a role in development of ASD phenotype. Further genetic and molecular studies are needed in this area.