Association of the α4 integrin subunit gene (ITGA4) with autism

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 150B; no. 8; pp. 1147 - 1151
• Main Authors: Correia, Catarina, Coutinho, Ana M., Almeida, Joana, Lontro, Raquel, Lobo, Cristina, Miguel, Teresa S., Martins, Madalena, Gallagher, Louise, Conroy, Judith, Gill, Michael, Oliveira, Guiomar, Vicente, Astrid M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05-12-2009; Wiley-Liss
• Subjects: autism; Biological and medical sciences; Child clinical studies; Developmental disorders; Infantile autism; ITGA4 gene; Medical genetics; Medical sciences; neuroimmune process; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Autism; Nervous system diseases; Association; Integrin; Gene; neuroimmune process; Genetics; Developmental disorder; ITGA4 gene; Subunit; Neurological disorder
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30940

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). α4 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. © 2009 Wiley‐Liss, Inc.