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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. Cyclooxygenases (COX) play a central role in the inşammatory cascade by converting arachidonic acid (AA), released from membrane phospholipids by a phospholipase A2 (PLA2), into bioactive prostanoids. Because COX-2 is typically induced by inşammatory stimuli in the majority of tissues, it was thought to be the only isoform responsible for propagating the inşammatory response and thus, considered as the best target for anti-inşammatory drugs. Recent findings suggest that COX-2-derived products can mediate a protective effect in the progression and/or the resolution of inşammation in the brain after endotoxin activation of brain innate immunity. There have been some reports on the role of COX-2 in pathophysiology of neurodegenerative (i.e. Alzheimer disease, multiple sclerosis) and neuropsychiatric disorders (i.e autism spectrum disorders). Several lines of evidence have been suggested between COX-2 and autism spectrum disorders (ASD). The aim of this study is to investigate COX-2 gene polymorphism in autism spectrum disorders.
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 Medical Faculty, 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 to sterile EDTA test tube for DNA isolation. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and agars gel electrophoresis are used to assess COX-2-765GıC and COX-2-1195AıG genes polymorphism in DNA samples. Genetic analysis was conducted in Istanbul University, Institute of Experimental Medicine (DETAE), Molecular Medicine Department. Family based approaches like transmission disequilibrium test (TDT) and haplotype-relative-risk (HRR) were used in data analysis.
Results: 101 subjects (16 girls, 15,8%; 85 boys, 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 COX-2-1195A gene and autism spectrum disorders (p: 0,0262). There is no significant association between COX-2-765G gene and ASD (p:0,2248).
Conclusion: The findings of this study may suggest that COX-2 genes, particularly COX-2-1195A might appears to be a viable candidate gene for the pathogenesis of autism and have a role development of ASD phenotype. Further genetic and molecular studies are needed on this area.