title: Association of the alpha4 integrin subunit gene (ITGA4) with autism.
abstract: In the present work, we provide further evidence for the involvement of the integrin alpha-4 precursor gene (ITGA4) in the etiology of autism, by replicating previous findings of a genetic association with autism in various independent populations. The ITGA4 gene maps to the autism linkage region on 2q31-33 and is therefore a plausible positional candidate. We tested eight single nucleotide polymorphisms (SNPs) in the ITGA4 gene region for association with autism in a sample of 164 nuclear families. Evidence for association was found for the rs155100 marker (P = 0.019) and for a number of specific marker haplotypes containing this SNP (0.00053 < P < 0.022). alpha4 integrins are known to play a key role in neuroinflammatory processes, which are hypothesized to contribute to autism. In this study, an association was found between the ITGA4 rs1449263 marker and levels of a serum autoantibody directed to brain tissue, which was previously shown to be significantly more frequent in autistic patients than in age-matched controls in our population. This result suggests that the ITGA4 gene could be involved in a neuroimmune process thought to occur in autistic patients and, together with previous findings, offers a new perspective on the role of integrins in the etiology of autism to which little attention has been paid so far.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Correia
authors.forename: Ana M
authors.initials: AM
authors.lastname: Coutinho
authors.forename: Joana
authors.initials: J
authors.lastname: Almeida
authors.forename: Raquel
authors.initials: R
authors.lastname: Lontro
authors.forename: Cristina
authors.initials: C
authors.lastname: Lobo
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Miguel
authors.forename: Madalena
authors.initials: M
authors.lastname: Martins
authors.forename: Louise
authors.initials: L
authors.lastname: Gallagher
authors.forename: Judith
authors.initials: J
authors.lastname: Conroy
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Guiomar
authors.initials: G
authors.lastname: Oliveira
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Vicente
mesh_terms: D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001921:Brain / Q000276:immunology; D002889:Chromosomes, Human, Pair 2; D005192:Family Health; D056726:Genetic Association Studies; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D039441:Integrin alpha4 / Q000235:genetics*; D020078:Neurogenic Inflammation; D015213:Neuroimmunomodulation; D020641:Polymorphism, Single Nucleotide
chemical_list: D001323:Autoantibodies; D005819:Genetic Markers; D039441:Integrin alpha4