title: The role of β3 integrin gene variants in Autism Spectrum Disorders--diagnosis and symptomatology.
abstract: Autism Spectrum Disorders (ASDs) represent a group of very complex early-onset neurodevelopmental diseases. In this study, we analyzed 5 SNPs (rs2317385, rs5918, rs15908, rs12603582, rs3809865) at the β3 integrin locus (ITGB3), which has been suggested as a possible susceptibility gene, both as single markers and as part of haplotypes in 209 ASD children and their biological parents. We tested for association with the following: a) DSM-IV ASD diagnosis; b) clinical symptoms common in ASD patients (repetitive behaviors, echolalia, seizures and epilepsy, mood instability, aggression, psychomotor agitation, sleep disorders); and c) dimensional scores obtained with the Autism Screening Questionnaire and the Childhood Autism Rating Scale. These hypotheses were investigated using family-based tests, logistic regression models and analysis of covariance. The family-based tests showed an association with the H5 haplotype (composed by GTCGA alleles, the order of SNPs as above), which was transmitted less often than expected by chance (P=0.006; Pcorr=0.036). The analyses of the clinical symptoms showed a trend for an association with rs12603582 (P=0.008; Pcorr=0.064) and positive results for the haplotype composed of rs15908 and rs12603582 (Pglcorr=0.048; Pindcorr=0.015), both in symptoms of echolalia. Other nominal associations with different variants were found and involved epilepsy/seizures, aggression symptoms and higher ASQ scores. Although our positive results are not definitive, they suggest small effect associations of the ITGB3 gene with both ASD diagnosis and symptoms of echolalia. Other studies are nonetheless needed to fully understand the involvement of this locus on the etiology of ASDs and its different clinical aspects.
authors.affiliation: Department of Genetics, Biosciences Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, 91501-970 Porto Alegre, Brazil. Electronic address: jaqbs.bio@gmail.com.
authors.forename: Jaqueline Bohrer
authors.initials: JB
authors.lastname: Schuch
authors.affiliation: Department of Genetics, Biosciences Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, 91501-970 Porto Alegre, Brazil.
authors.forename: Diana
authors.initials: D
authors.lastname: Muller
authors.affiliation: Department of Psychology, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2600, 90035-003 Porto Alegre, Brazil.
authors.forename: Renata Giuliani
authors.initials: RG
authors.lastname: Endres
authors.affiliation: Department of Psychology, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2600, 90035-003 Porto Alegre, Brazil. Electronic address: cleobosa@uol.com.br.
authors.forename: Cleonice Alves
authors.initials: CA
authors.lastname: Bosa
authors.affiliation: Department of Genetics, Biosciences Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, 91501-970 Porto Alegre, Brazil.
authors.forename: Dânae
authors.initials: D
authors.lastname: Longo
authors.affiliation: Department of Genetics, Biosciences Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, 91501-970 Porto Alegre, Brazil.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Schuler-Faccini
authors.affiliation: Child Neurology Unit, Clinics Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, Brazil.
authors.forename: Josiane
authors.initials: J
authors.lastname: Ranzan
authors.affiliation: Child Neurology Unit, Clinics Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, Brazil.
authors.forename: Michele Michelin
authors.initials: MM
authors.lastname: Becker
authors.affiliation: Child Neurology Unit, Clinics Hospital of Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, Brazil. Electronic address: rriesgo@hcpa.ufrgs.br.
authors.forename: Rudimar
authors.initials: R
authors.lastname: dos Santos Riesgo
authors.affiliation: Department of Genetics, Biosciences Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, 91501-970 Porto Alegre, Brazil. Electronic address: troman29@yahoo.com.br.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Roman
mesh_terms: D000293:Adolescent; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male
chemical_list: D039661:Integrin beta3
keywords: ASD; Association; Autism; Clinical symptoms; Echolalia; ITGB3 gene