title: DNA repair gene XPD Asp312Asn and XRCC4 G-1394T polymorphisms and the risk of autism spectrum disorder.
abstract: Autism spectrum disorder (ASD) is a complex disorder, and its extreme heterogeneity further complicates our understanding of its biology. Epidemiological evidence from family and twin studies supports a strong genetic component in ASD etiology. Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of ASD. Brain tissues from ASD cases showed higher levels of oxidative stress biomarkers than healthy controls in postmortem analysis. Association between oxidative stress and DNA damage has been well-known. Thus, we sought to investigate a potential link between DNA repair genes and ASD and analyze the role of XPD Asp312Asn and XRCC4 G-1394T gene polymorphisms for ASD in the Turkish population. Genotyping was conducted by PCR-RFLP based on 100 patients and 96 unrelated healthy controls. We, for the first time, demonstrated a positive association between XRCC4 gene variants and ASD risk. Frequencies of XRCC4-1394 T/G+G/G genotypes were higher in patients (%34) than the controls (%18.7). The statistical analysis revealed that the individuals who had XRCC4-1394 T/G+G/G genotype had an increased risk for ASD (OR = 2.23, 95% CI = 1.10-4.55). However, no significant association was found for XPD Asp312Asn polymorphism with the risk of ASD. Our findings suggest that XRCC4 G-1394T polymorphism might be associated with ASD pathogenesis.
authors.affiliation: University of Istanbul Department of Medical Genetics, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Dasdemir
authors.affiliation: University of Istanbul Department of Medical Biology, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Guven
authors.affiliation: University of Istanbul Department of Medical Genetics, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: K C
authors.initials: KC
authors.lastname: Pekkoc
authors.affiliation: University of Istanbul Department of Medical Genetics, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Ulucan
authors.affiliation: University of Istanbul Department of Child and Adolescent Psychiatry, Cerrahpasa Faculty of Medicine Istanbul Turkey burakdogangun@hotmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Dogangun
authors.affiliation: University of Istanbul Department of Child and Adolescent Psychiatry, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Kirtas
authors.affiliation: University of Istanbul Department of Child and Adolescent Psychiatry, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: M T
authors.initials: MT
authors.lastname: Kadak
authors.affiliation: University of Istanbul Department of Biochemistry, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Kucur
authors.affiliation: University of Istanbul Department of Medical Genetics, Cerrahpasa Faculty of Medicine Istanbul Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Seven
mesh_terms: D000067877:Autism Spectrum Disorder / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D014421:Turkey / Q000453:epidemiology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C101467:XRCC4 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human